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Annual Review of Immunology

Volume 41, 2023

IL-4 and IL-13: Regulators and Effectors of Wound Repair

Abstract

Type 2 immunity mediates protective responses to helminths and pathological responses to allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. Type 2 cytokines are known to promote fibrosis, an overzealous repair response, but their contribution to healthy wound repair is less well understood. This review discusses the evidence that the canonical type 2 cytokines, IL-4 and IL-13, are integral to the tissue repair process through two main pathways. First, essential for the progression of effective tissue repair, IL-4 and IL-13 suppress the initial inflammatory response to injury. Second, these cytokines regulate how the extracellular matrix is modified, broken down, and rebuilt for effective repair. IL-4 and/or IL-13 amplifies multiple aspects of the tissue repair response, but many of these pathways are highly redundant and can be induced by other signals. Therefore, the exact contribution of IL-4Rα signaling remains difficult to unravel.

Keyword(s): extracellular matrix, helminths, inflammation, tissue injury, type 2 immunity
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/content/journals/10.1146/annurev-immunol-101921-041206
2023-04-26
2024-04-25
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Literature Cited

  1. 1.
    Iwasaki A, Medzhitov R. 2015. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16:4343–53
     [Google Scholar]
  2. 2.
    Hammad H, Debeuf N, Aegerter H, Brown AS, Lambrecht BN. 2022. Emerging paradigms in type 2 immunity. Annu. Rev. Immunol. 40:443–67
     [Google Scholar]
  3. 3.
    Allen JE, Maizels RM. 2011. Diversity and dialogue in immunity to helminths. Nat. Rev. Immunol. 11:6375–88
     [Google Scholar]
  4. 4.
    Eming SA, Krieg T, Davidson JM. 2007. Inflammation in wound repair: molecular and cellular mechanisms. J. Investig. Dermatol. 127:3514–25
     [Google Scholar]
  5. 5.
    Graham AL, Allen JE, Read AF. 2005. Evolutionary causes and consequences of immunopathology. Annu. Rev. Ecol. Evol. Syst. 36:1373–97
     [Google Scholar]
  6. 6.
    Allen JE, Sutherland TE. 2014. Host protective roles of type 2 immunity: parasite killing and tissue repair, flip sides of the same coin. Semin. Immunol. 26:4329–40
     [Google Scholar]
  7. 7.
    Allen JE, Wynn TA. 2011. Evolution of Th2 immunity: a rapid repair response to tissue destructive pathogens. PLOS Pathog. 7:5e1002003
     [Google Scholar]
  8. 8.
    Medzhitov R. 2021. The spectrum of inflammatory responses. Science 374:65711070–75
     [Google Scholar]
  9. 9.
    Herbert DR, Hölscher C, Mohrs M, Arendse B, Schwegmann A et al. 2004. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20:5623–35
     [Google Scholar]
  10. 10.
    Sutherland TE, Rückerl D, Logan N, Duncan S, Wynn TA, Allen JE. 2018. Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection. PLOS Pathog. 14:11e1007423
     [Google Scholar]
  11. 11.
    Chen F, Liu Z, Wu W, Rozo C, Bowdridge S et al. 2012. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat. Med. 18:2260–66
     [Google Scholar]
  12. 12.
    Chenery AL, Rosini S, Parkinson JE, Ajendra J, Herrera JA et al. 2021. IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection. Life Sci. Alliance 4:8e202001000
     [Google Scholar]
  13. 13.
    Walter J, Kovalenko O, Younsi A, Grutza M, Unterberg A, Zweckberger K. 2022. Interleukin-4 reduces lesion volume and improves neurological function in the acute phase after experimental traumatic brain injury in mice. J. Neurotrauma 39:17–181262–72
     [Google Scholar]
  14. 14.
    Knipper JA, Willenborg S, Brinckmann J, Bloch W, Maaß T et al. 2015. Interleukin-4 receptor α signaling in myeloid cells controls collagen fibril assembly in skin repair. Immunity 43:4803–16
     [Google Scholar]
  15. 15.
    Heredia JE, Mukundan L, Chen FM, Mueller AA, Deo RC et al. 2013. Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell 153:2376–88
     [Google Scholar]
  16. 16.
    Sadtler K, Estrellas K, Allen BW, Wolf MT, Fan H et al. 2016. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science 352:6283366–70
     [Google Scholar]
  17. 17.
    Hofmann U, Knorr S, Vogel B, Weirather J, Frey A et al. 2014. Interleukin-13 deficiency aggravates healing and remodeling in male mice after experimental myocardial infarction. Circ. Heart Fail. 7:5822–30
     [Google Scholar]
  18. 18.
    Qian N, Gao Y, Wang J, Wang Y 2021. Emerging role of interleukin-13 in cardiovascular diseases: a ray of hope. J. Cell. Mol. Med. 25:125351–57
     [Google Scholar]
  19. 19.
    Xiong X, Barreto GE, Xu L, Ouyang YB, Xie X, Giffard RG. 2011. Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke 42:72026–32
     [Google Scholar]
  20. 20.
    Pan D, Schellhardt L, Acevedo-Cintron JA, Hunter D, Snyder-Warwick AK et al. 2022. IL-4 expressing cells are recruited to nerve after injury and promote regeneration. Exp. Neurol. 347:113909
     [Google Scholar]
  21. 21.
    Lechner AJ, Driver IH, Lee J, Conroy CM, Nagle A et al. 2017. Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy. Cell Stem Cell 21:120–34.e7
     [Google Scholar]
  22. 22.
    Hearn AP, Kent BD, Jackson DJ. 2020. Biologic treatment options for severe asthma. Curr. Opin. Immunol. 66:151–60
     [Google Scholar]
  23. 23.
    Goldman JA, Poss KD. 2020. Gene regulatory programmes of tissue regeneration. Nat. Rev. Genet. 21:9511–25
     [Google Scholar]
  24. 24.
    Eming SA, Martin P, Tomic-Canic M. 2014. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med. 6:265265sr6
     [Google Scholar]
  25. 25.
    Henderson NC, Rieder F, Wynn TA. 2020. Fibrosis: from mechanisms to medicines. Nature 587:7835555–66
     [Google Scholar]
  26. 26.
    Cash JL, Martin P. 2016. Myeloid cells in cutaneous wound repair. Microbiol Spectr. 4:3 https://doi.org/10.1128/microbiolspec.MCHD-0017-2015
    [Google Scholar]
  27. 27.
    Gieseck RL 3rd, Wilson MS, Wynn TA. 2018. Type 2 immunity in tissue repair and fibrosis. Nat. Rev. Immunol. 18:162–76
     [Google Scholar]
  28. 28.
    Reinke JM, Sorg H. 2012. Wound repair and regeneration. Eur. Surg. Res. 49:135–43
     [Google Scholar]
  29. 29.
    Minutti CM, Knipper JA, Allen JE, Zaiss DMW. 2017. Tissue-specific contribution of macrophages to wound healing. Semin. Cell Dev. Biol. 61:3–11
     [Google Scholar]
  30. 30.
    Mahdavian Delavary B, van der Veer WM, van Egmond M, Niessen FB, Beelen RHJ 2011. Macrophages in skin injury and repair. Immunobiology 216:7753–62
     [Google Scholar]
  31. 31.
    Oncel S, Basson MD. 2022. Gut homeostasis, injury, and healing: new therapeutic targets. World J. Gastroenterol. 28:171725–50
     [Google Scholar]
  32. 32.
    Vannella KM, Wynn TA. 2017. Mechanisms of organ injury and repair by macrophages. Annu. Rev. Physiol. 79:593–617
     [Google Scholar]
  33. 33.
    Beers MF, Morrisey EE. 2011. The three R's of lung health and disease: repair, remodeling, and regeneration. J. Clin. Investig. 121:62065–73
     [Google Scholar]
  34. 34.
    Albina JE, Mills CD, Henry WL Jr., Caldwell MD. 1990. Temporal expression of different pathways of 1-arginine metabolism in healing wounds. J. Immunol. 144:103877–80
     [Google Scholar]
  35. 35.
    Albina JE, Mills CD, Barbul A, Thirkill CE, Henry WL Jr. et al. 1988. Arginine metabolism in wounds. Am. J. Physiol. 254:4 Part 1E459–67
     [Google Scholar]
  36. 36.
    Munder M, Eichmann K, Modolell M. 1998. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype. J. Immunol. 160:115347–54
     [Google Scholar]
  37. 37.
    Loke P, Nair MG, Parkinson J, Guiliano D, Blaxter M, Allen JE. 2002. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype. BMC Immunol. 3:7
     [Google Scholar]
  38. 38.
    Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM et al. 2001. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: Granulomatous pathology is shaped by the pattern of l-arginine metabolism. J. Immunol. 167:116533–44
     [Google Scholar]
  39. 39.
    Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. 2000. M-1/M-2 macrophages and the Th1/Th2 paradigm. J. Immunol. 164:126166–73
     [Google Scholar]
  40. 40.
    Lucas T, Waisman A, Ranjan R, Roes J, Krieg T et al. 2010. Differential roles of macrophages in diverse phases of skin repair. J. Immunol. 184:73964–77
     [Google Scholar]
  41. 41.
    Junttila IS, Mizukami K, Dickensheets H, Meier-Schellersheim M, Yamane H et al. 2008. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rα, IL-13Rα1, and γc regulates relative cytokine sensitivity. J. Exp. Med. 205:112595–608
     [Google Scholar]
  42. 42.
    Junttila IS. 2018. Tuning the cytokine responses: an update on interleukin (IL)-4 and IL-13 receptor complexes. Front. Immunol. 9:888
     [Google Scholar]
  43. 43.
    Heeb LEM, Boyman O. 2022. Comprehensive analysis of human IL-4 receptor subunits shows compartmentalization in steady state and dupilumab treatment. Allergy https://doi.org/10.1111/all.15576
    [Google Scholar]
  44. 44.
    Amit U, Kain D, Wagner A, Sahu A, Nevo-Caspi Y et al. 2017. New role for interleukin-13 receptor α1 in myocardial homeostasis and heart failure. J. Am. Heart Assoc. 6:5e005108
     [Google Scholar]
  45. 45.
    Roy S, Liu H-Y, Jaeson MI, Deimel LP, Ranasinghe C. 2020. Unique IL-13Rα2/STAT3 mediated IL-13 regulation detected in lung conventional dendritic cells, 24 h post viral vector vaccination. Sci. Rep. 10:11017
     [Google Scholar]
  46. 46.
    Zheng T, Liu W, Oh S-Y, Zhu Z, Hu B et al. 2008. IL-13 receptor α2 selectively inhibits IL-13-induced responses in the murine lung. J. Immunol. 180:1522–29
     [Google Scholar]
  47. 47.
    Sutherland TE, Logan N, Rückerl D, Humbles AA, Allan SM et al. 2014. Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage. Nat. Immunol. 15:121116–25
     [Google Scholar]
  48. 48.
    Krljanac B, Schubart C, Naumann R, Wirtz S, Culemann S et al. 2019. RELMα-expressing macrophages protect against fatal lung damage and reduce parasite burden during helminth infection. Sci Immunol. 4:35eaau3814
     [Google Scholar]
  49. 49.
    Goerdt S, Orfanos CE. 1999. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity 10:2137–42
     [Google Scholar]
  50. 50.
    Thomas GD, Rückerl D, Maskrey BH, Whitfield PD, Blaxter ML, Allen JE. 2012. The biology of nematode- and IL4Rα-dependent murine macrophage polarization in vivo as defined by RNA-Seq and targeted lipidomics. Blood 120:25e93–104
     [Google Scholar]
  51. 51.
    Loke P, Gallagher I, Nair MG, Zang X, Brombacher F et al. 2007. Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection. J. Immunol. 179:63926–36
     [Google Scholar]
  52. 52.
    Daseke MJ 2nd, Tenkorang-Impraim MAA, Ma Y, Chalise U, Konfrst SR et al. 2020. Exogenous IL-4 shuts off pro-inflammation in neutrophils while stimulating anti-inflammation in macrophages to induce neutrophil phagocytosis following myocardial infarction. J. Mol. Cell. Cardiol. 145:112–21
     [Google Scholar]
  53. 53.
    Impellizzieri D, Ridder F, Raeber ME, Egholm C, Woytschak J et al. 2019. IL-4 receptor engagement in human neutrophils impairs their migration and extracellular trap formation. J. Allergy Clin. Immunol. 144:1267–79
     [Google Scholar]
  54. 54.
    Ajendra J. 2021. Lessons in type 2 immunity: neutrophils in helminth infections. Semin. Immunol. 53:101531
     [Google Scholar]
  55. 55.
    Woytschak J, Keller N, Krieg C, Impellizzieri D, Thompson RW et al. 2016. Type 2 interleukin-4 receptor signaling in neutrophils antagonizes their expansion and migration during infection and inflammation. Immunity 45:1172–84
     [Google Scholar]
  56. 56.
    Morgan AH, Dioszeghy V, Maskrey BH, Thomas CP, Clark SR et al. 2009. Phosphatidylethanolamine-esterified eicosanoids in the mouse: tissue localization and inflammation-dependent formation in Th-2 disease. J. Biol. Chem. 284:3221185–91
     [Google Scholar]
  57. 57.
    Seno H, Miyoshi H, Brown SL, Geske MJ, Colonna M, Stappenbeck TS. 2009. Efficient colonic mucosal wound repair requires Trem2 signaling. PNAS 106:1256–61
     [Google Scholar]
  58. 58.
    Salmon-Ehr V, Ramont L, Godeau G, Birembaut P, Guenounou M et al. 2000. Implication of interleukin-4 in wound healing. Lab. Investig. 80:81337–43
     [Google Scholar]
  59. 59.
    Bugler-Lamb A, Guilliams M. 2020. Myeloid cells TREM down anti-tumor responses. Cell 182:4796–98
     [Google Scholar]
  60. 60.
    Eming SA, Murray PJ, Pearce EJ. 2021. Metabolic orchestration of the wound healing response. Cell Metab. 33:91726–43
     [Google Scholar]
  61. 61.
    Galván-Peña S, O'Neill LAJ 2014. Metabolic reprograming in macrophage polarization. Front. Immunol. 5:420
     [Google Scholar]
  62. 62.
    Pearce EL, Pearce EJ. 2013. Metabolic pathways in immune cell activation and quiescence. Immunity 38:4633–43
     [Google Scholar]
  63. 63.
    Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL et al. 2006. Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab. 4:13–24
     [Google Scholar]
  64. 64.
    McGettrick AF, O'Neill LAJ 2013. How metabolism generates signals during innate immunity and inflammation. J. Biol. Chem. 288:3222893–98
     [Google Scholar]
  65. 65.
    Willenborg S, Lucas T, van Loo G, Knipper JA, Krieg T et al. 2012. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood 120:3613–25
     [Google Scholar]
  66. 66.
    Cameron AM, Castoldi A, Sanin DE, Flachsmann LJ, Field CS et al. 2019. Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species-mediated DNA damage. Nat. Immunol. 20:4420–32
     [Google Scholar]
  67. 67.
    Szondi DC, Wong JK, Vardy LA, Cruickshank SM. 2021. Arginase signalling as a key player in chronic wound pathophysiology and healing. Front. Mol Biosci. 8:773866
     [Google Scholar]
  68. 68.
    Martí i Líndez A-A, Reith W. 2021. Arginine-dependent immune responses. Cell. Mol. Life Sci. 78:135303–24
     [Google Scholar]
  69. 69.
    Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J et al. 2003. l-Arginine consumption by macrophages modulates the expression of CD3ζ chain in T lymphocytes. J. Immunol. 171:31232–39
     [Google Scholar]
  70. 70.
    Herbert DR, Orekov T, Roloson A, Ilies M, Perkins C et al. 2010. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J. Immunol. 184:116438–46
     [Google Scholar]
  71. 71.
    Campbell L, Saville CR, Murray PJ, Cruickshank SM, Hardman MJ. 2013. Local arginase 1 activity is required for cutaneous wound healing. J. Investig. Dermatol. 133:102461–70
     [Google Scholar]
  72. 72.
    Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC et al. 2009. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLOS Pathog. 5:4e1000371
     [Google Scholar]
  73. 73.
    Iniesta V, Gómez-Nieto LC, Molano I, Mohedano A, Carcelén J et al. 2002. Arginase I induction in macrophages, triggered by Th2-type cytokines, supports the growth of intracellular Leishmania parasites. Parasite Immunol. 24:3113–18
     [Google Scholar]
  74. 74.
    Dichtl S, Lindenthal L, Zeitler L, Behnke K, Schlösser D et al. 2021. Lactate and IL6 define separable paths of inflammatory metabolic adaptation. Sci. Adv. 7:26eabg3505
     [Google Scholar]
  75. 75.
    Mylonas KJ, Nair MG, Prieto-Lafuente L, Paape D, Allen JE. 2009. Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing. J. Immunol. 182:53084–94
     [Google Scholar]
  76. 76.
    Colegio OR, Chu N-Q, Szabo AL, Chu T, Rhebergen AM et al. 2014. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513:7519559–63
     [Google Scholar]
  77. 77.
    Jinnin M, Ihn H, Yamane K, Tamaki K. 2004. Interleukin-13 stimulates the transcription of the human α2(I) collagen gene in human dermal fibroblasts. J. Biol. Chem. 279:4041783–91
     [Google Scholar]
  78. 78.
    Oriente A, Fedarko NS, Pacocha SE, Huang SK, Lichtenstein LM, Essayan DM. 2000. Interleukin-13 modulates collagen homeostasis in human skin and keloid fibroblasts. J. Pharmacol. Exp. Ther. 292:3988–94
     [Google Scholar]
  79. 79.
    Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX. 1991. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell. Mol. Biol. 37:8823–29
     [Google Scholar]
  80. 80.
    Sempowski GD, Beckmann MP, Derdak S, Phipps RP. 1994. Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors: role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. J. Immunol. 152:73606–14
     [Google Scholar]
  81. 81.
    Hoffmann KF, McCarty TC, Segal DH, Chiaramonte M, Hesse M et al. 2001. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. FASEB J. 15:132545–47
     [Google Scholar]
  82. 82.
    Gratchev A, Guillot P, Hakiy N, Politz O, Orfanos CE et al. 2001. Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein βIG-H3. Scand. J. Immunol. 53:4386–92
     [Google Scholar]
  83. 83.
    Gratchev A, Kzhyshkowska J, Utikal J, Goerdt S. 2005. Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages. Scand. J. Immunol. 61:110–17
     [Google Scholar]
  84. 84.
    Schnoor M, Cullen P, Lorkowski J, Stolle K, Robenek H et al. 2008. Production of type VI collagen by human macrophages: a new dimension in macrophage functional heterogeneity. J. Immunol. 180:85707–19
     [Google Scholar]
  85. 85.
    Madala SK, Pesce JT, Ramalingam TR, Wilson MS, Minnicozzi S et al. 2010. Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J. Immunol. 184:73955–63
     [Google Scholar]
  86. 86.
    Weng S-Y, Wang X, Vijayan S, Tang Y, Kim YO et al. 2018. IL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal. EBioMedicine 29:92–103
     [Google Scholar]
  87. 87.
    Goh YPS, Henderson NC, Heredia JE, Red Eagle A, Odegaard JI et al. 2013. Eosinophils secrete IL-4 to facilitate liver regeneration. PNAS 110:249914–19
     [Google Scholar]
  88. 88.
    Ignacio A, Shah K, Bernier-Latmani J, Köller Y, Coakley G et al. 2022. Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization. Immunity 55:71250–67.e12
     [Google Scholar]
  89. 89.
    Doyle AD, Mukherjee M, LeSuer WE, Bittner TB, Pasha SM et al. 2019. Eosinophil-derived IL-13 promotes emphysema. Eur. Respir. J. 53:51801291
     [Google Scholar]
  90. 90.
    Voehringer D, van Rooijen N, Locksley RM. 2007. Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages. J. Leukoc. Biol. 81:61434–44
     [Google Scholar]
  91. 91.
    Karamanos NK, Theocharis AD, Piperigkou Z, Manou D, Passi A et al. 2021. A guide to the composition and functions of the extracellular matrix. FEBS J. 288:246850–912
     [Google Scholar]
  92. 92.
    Sutherland TS, Dyer D, Allen JE. 2022. The extracellular matrix and the immune system: a mutually dependent relationship. Science 379:6633eabp8964
     [Google Scholar]
  93. 93.
    Frevert CW, Felgenhauer J, Wygrecka M, Nastase MV, Schaefer L. 2018. Danger-associated molecular patterns derived from the extracellular matrix provide temporal control of innate immunity. J. Histochem. Cytochem. 66:4213–27
     [Google Scholar]
  94. 94.
    Gray AL, Pun N, Ridley AJL, Dyer DP. 2022. Role of extracellular matrix proteoglycans in immune cell recruitment. Int. J. Exp. Pathol. 103:234–43
     [Google Scholar]
  95. 95.
    Wight TN. 2017. Provisional matrix: a role for versican and hyaluronan. Matrix Biol. 60–61 38–56
     [Google Scholar]
  96. 96.
    Motz GT, Coukos G. 2011. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat. Rev. Immunol. 11:10702–11
     [Google Scholar]
  97. 97.
    Erickson JR, Echeverri K. 2018. Learning from regeneration research organisms: the circuitous road to scar free wound healing. Dev. Biol. 433:2144–54
     [Google Scholar]
  98. 98.
    Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B et al. 2000. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J. Clin. Investig. 106:91081–93
     [Google Scholar]
  99. 99.
    Pouladi MA, Robbins CS, Swirski FK, Cundall M, McKenzie ANJ et al. 2004. Interleukin-13-dependent expression of matrix metalloproteinase-12 is required for the development of airway eosinophilia in mice. Am. J. Respir. Cell Mol. Biol. 30:184–90
     [Google Scholar]
  100. 100.
    Bellac CL, Dufour A, Krisinger MJ, Loonchanta A, Starr AE et al. 2014. Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis. Cell Rep. 9:2618–32
     [Google Scholar]
  101. 101.
    Hart KM, Fabre T, Sciurba JC, Gieseck RL 3rd, Borthwick LA et al. 2017. Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β. Sci. Transl. Med. 9:396eaal3694
     [Google Scholar]
  102. 102.
    Ramalingam TR, Gieseck RL, Acciani TH, Hart KM, Cheever AW et al. 2016. Enhanced protection from fibrosis and inflammation in the combined absence of IL-13 and IFN-γ. J. Pathol. 239:3344–54
     [Google Scholar]
  103. 103.
    Schuster R, Rockel JS, Kapoor M, Hinz B. 2021. The inflammatory speech of fibroblasts. Immunol. Rev. 302:1126–46
     [Google Scholar]
  104. 104.
    Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X et al. 2001. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor β1. J. Exp. Med. 194:6809–21
     [Google Scholar]
  105. 105.
    Gieseck RL 3rd, Ramalingam TR, Hart KM, Vannella KM, Cantu DA et al. 2016. Interleukin-13 activates distinct cellular pathways leading to ductular reaction, steatosis, and fibrosis. Immunity 45:1145–58
     [Google Scholar]
  106. 106.
    O'Reilly S, Ciechomska M, Fullard N, Przyborski S, van Laar JM. 2016. IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics. Sci. Rep. 6:25066
     [Google Scholar]
  107. 107.
    Kolodsick JE, Toews GB, Jakubzick C, Hogaboam C, Moore TA et al. 2004. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J. Immunol. 172:74068–76
     [Google Scholar]
  108. 108.
    Simões FC, Cahill TJ, Kenyon A, Gavriouchkina D, Vieira JM et al. 2020. Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair. Nat. Commun. 11:1600
     [Google Scholar]
  109. 109.
    Cescon M, Gattazzo F, Chen P, Bonaldo P. 2015. Collagen VI at a glance. J. Cell Sci. 128:193525–31
     [Google Scholar]
  110. 110.
    Singampalli KL, Balaji S, Wang X, Parikh UM, Kaul A et al. 2020. The role of an IL-10/hyaluronan axis in dermal wound healing. Front. Cell Dev. Biol. 8:636
     [Google Scholar]
  111. 111.
    Theocharidis G, Drymoussi Z, Kao AP, Barber AH, Lee DA et al. 2016. Type VI collagen regulates dermal matrix assembly and fibroblast motility. J. Investig. Dermatol. 136:74–83
     [Google Scholar]
  112. 112.
    Sanin DE, Matsushita M, Klein Geltink RI, Grzes KM, van Teijlingen Bakker N et al. 2018. Mitochondrial membrane potential regulates nuclear gene expression in macrophages exposed to prostaglandin E2. Immunity 49:61021–33.e6
     [Google Scholar]
  113. 113.
    Pakshir P, Hinz B. 2018. The big five in fibrosis: macrophages, myofibroblasts, matrix, mechanics, and miscommunication. Matrix Biol. 68–69 81–93
     [Google Scholar]
  114. 114.
    Lodyga M, Cambridge E, Karvonen HM, Pakshir P, Wu B et al. 2019. Cadherin-11-mediated adhesion of macrophages to myofibroblasts establishes a profibrotic niche of active TGF-β. Sci. Signal. 12:564eaao3469
     [Google Scholar]
  115. 115.
    Adler M, Mayo A, Zhou X, Franklin RA, Meizlish ML et al. 2020. Principles of cell circuits for tissue repair and fibrosis. iScience 23:2100841
     [Google Scholar]
  116. 116.
    Willenborg S, Sanin DE, Jais A, Ding X, Ulas T et al. 2021. Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metab. 33:122398–414.e9
     [Google Scholar]
  117. 117.
    Zaiss DM, Yang L, Shah PR, Kobie JJ, Urban JF, Mosmann TR. 2006. Amphiregulin, a TH2 cytokine enhancing resistance to nematodes. Science 314:58061746
     [Google Scholar]
  118. 118.
    Zaiss DMW, Gause WC, Osborne LC, Artis D. 2015. Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair. Immunity 42:2216–26
     [Google Scholar]
  119. 119.
    Donlan AN, Sutherland TE, Marie C, Preissner S, Bradley BT et al. 2021. IL-13 is a driver of COVID-19 severity. JCI Insight 6:15eaao3469
     [Google Scholar]
  120. 120.
    Turner J-E, Morrison PJ, Wilhelm C, Wilson M, Ahlfors H et al. 2013. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J. Exp. Med. 210:132951–65
     [Google Scholar]
  121. 121.
    Minutti CM, Modak RV, Macdonald F, Li F, Smyth DJ et al. 2019. A macrophage-pericyte axis directs tissue restoration via amphiregulin-induced transforming growth factor beta activation. Immunity 50:3645–54.e6
     [Google Scholar]
  122. 122.
    Chen F, Wu W, Jin L, Millman A, Palma M et al. 2018. B cells produce the tissue-protective protein RELMα during helminth infection, which inhibits IL-17 expression and limits emphysema. Cell Rep. 25:102775–83.e3
     [Google Scholar]
  123. 123.
    Nair MG, Du Y, Perrigoue JG, Zaph C, Taylor JJ et al. 2009. Alternatively activated macrophage-derived RELM-α is a negative regulator of type 2 inflammation in the lung. J. Exp. Med. 206:4937–52
     [Google Scholar]
  124. 124.
    Parkinson JE, Pearson S, Rückerl D, Allen JE, Sutherland TE. 2021. The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs. Immunol. Cell Biol. 99:6640–55
     [Google Scholar]
  125. 125.
    Sutherland TE. 2018. Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?. Biochem. Soc. Trans. 46:1141–51
     [Google Scholar]
  126. 126.
    Day AJ, de la Motte CA. 2005. Hyaluronan cross-linking: a protective mechanism in inflammation?. Trends Immunol. 26:12637–43
     [Google Scholar]
  127. 127.
    Erickson M, Stern R. 2012. Chain gangs: new aspects of hyaluronan metabolism. Biochem. Res. Int. 2012:893947
     [Google Scholar]
  128. 128.
    Teder P, Vandivier RW, Jiang D, Liang J, Cohn L et al. 2002. Resolution of lung inflammation by CD44. Science 296:5565155–58
     [Google Scholar]
  129. 129.
    Hellman U, Karlsson MG, Engström-Laurent A, Cajander S, Dorofte L et al. 2020. Presence of hyaluronan in lung alveoli in severe Covid-19: an opening for new treatment options?. J. Biol. Chem. 295:4515418–22
     [Google Scholar]
  130. 130.
    Bell TJ, Brand OJ, Morgan DJ, Salek-Ardakani S, Jagger C et al. 2019. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 80:14–28
     [Google Scholar]
  131. 131.
    Reeves SR, Kang I, Chan CK, Barrow KA, Kolstad TK et al. 2018. Asthmatic bronchial epithelial cells promote the establishment of a hyaluronan-enriched, leukocyte-adhesive extracellular matrix by lung fibroblasts. Respir. Res. 19:1146
     [Google Scholar]
  132. 132.
    Zhuo L, Kanamori A, Kannagi R, Itano N, Wu J et al. 2006. SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. J. Biol. Chem. 281:2920303–14
     [Google Scholar]
  133. 133.
    Burdick JA, Prestwich GD. 2011. Hyaluronic acid hydrogels for biomedical applications. Adv. Mater. 23:12H41–56
     [Google Scholar]
  134. 134.
    Meran S, Luo DD, Simpson R, Martin J, Wells A et al. 2011. Hyaluronan facilitates transforming growth factor-β1-dependent proliferation via CD44 and epidermal growth factor receptor interaction. J. Biol. Chem. 286:2017618–30
     [Google Scholar]
  135. 135.
    Todd JL, Kelly FL, Nagler A, Banner K, Pavlisko EN et al. 2020. Amphiregulin contributes to airway remodeling in chronic allograft dysfunction after lung transplantation. Am. J. Transplant. 20:3825–33
     [Google Scholar]
  136. 136.
    Jha AK, Huang SC-C, Sergushichev A, Lampropoulou V, Ivanova Y et al. 2015. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:3419–30
     [Google Scholar]
  137. 137.
    Taylor KR, Gallo RL. 2006. Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation. FASEB J. 20:19–22
     [Google Scholar]
  138. 138.
    Melrose J. 2016. Glycosaminoglycans in wound healing. Bone Tissue Regen. Insights 7: https://doi.org/10.4137/BTRI.S38670
    [Google Scholar]
  139. 139.
    Kosir MA, Quinn CC, Wang W, Tromp G. 2000. Matrix glycosaminoglycans in the growth phase of fibroblasts: more of the story in wound healing. J. Surg. Res. 92:145–52
     [Google Scholar]
  140. 140.
    Migliorini E, Thakar D, Kühnle J, Sadir R, Dyer DP et al. 2015. Cytokines and growth factors cross-link heparan sulfate. Open Biol. 5:8150046
     [Google Scholar]
  141. 141.
    Dyer DP, Salanga CL, Volkman BF, Kawamura T, Handel TM. 2016. The dependence of chemokine-glycosaminoglycan interactions on chemokine oligomerization. Glycobiology 26:3312–26
     [Google Scholar]
  142. 142.
    Martinez P, Denys A, Delos M, Sikora A-S, Carpentier M et al. 2015. Macrophage polarization alters the expression and sulfation pattern of glycosaminoglycans. Glycobiology 25:5502–13
     [Google Scholar]
  143. 143.
    Soares da Costa D, Reis RL, Pashkuleva I. 2017. Sulfation of glycosaminoglycans and its implications in human health and disorders. Annu. Rev. Biomed. Eng. 19:1–26
     [Google Scholar]
  144. 144.
    Hasnain SZ, Dawson PA, Lourie R, Hutson P, Tong H et al. 2017. Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion. PLOS Pathog. 13:2e1006218
     [Google Scholar]
  145. 145.
    Webb DC, McKenzie AN, Foster PS. 2001. Expression of the Ym2 lectin-binding protein is dependent on interleukin (IL)-4 and IL-13 signal transduction: identification of a novel allergy-associated protein. J. Biol. Chem. 276:4541969–76
     [Google Scholar]
  146. 146.
    Finkelman FD, Shea-Donohue T, Morris SC, Gildea L, Strait R et al. 2004. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol. Rev. 201:139–55
     [Google Scholar]
  147. 147.
    Ridley C, Thornton DJ. 2018. Mucins: the frontline defence of the lung. Biochem. Soc. Trans. 46:51099–106
     [Google Scholar]
  148. 148.
    Wagner CE, Wheeler KM, Ribbeck K. 2018. Mucins and their role in shaping the functions of mucus barriers. Annu. Rev. Cell Dev. Biol. 34:189–215
     [Google Scholar]
  149. 149.
    Hasnain SZ, Evans CM, Roy M, Gallagher AL, Kindrachuk KN et al. 2011. Muc5ac: a critical component mediating the rejection of enteric nematodes. J. Exp. Med. 208:5893–900
     [Google Scholar]
  150. 150.
    Koropatkin NM, Cameron EA, Martens EC. 2012. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10:5323–35
     [Google Scholar]
  151. 151.
    Luis AS, Jin C, Pereira GV, Glowacki RWP, Gugel SR et al. 2021. A single sulfatase is required to access colonic mucin by a gut bacterium. Nature 598:7880332–37
     [Google Scholar]
  152. 152.
    Corfield AP. 2015. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim. Biophys. Acta. Gen. Subj. 1850:1236–52
     [Google Scholar]
  153. 153.
    Mashimo H, Wu DC, Podolsky DK, Fishman MC. 1996. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 274:5285262–65
     [Google Scholar]
  154. 154.
    Rossi HL, Ortiz-Carpena JF, Tucker D, Vaughan AE, Mangalmurti NS et al. 2022. Trefoil factor family: a troika for lung repair and regeneration. Am. J. Respir. Cell Mol. Biol. 66:3252–59
     [Google Scholar]
  155. 155.
    Thim L, Madsen F, Poulsen SS. 2002. Effect of trefoil factors on the viscoelastic properties of mucus gels. Eur. J. Clin. Investig. 32:7519–27
     [Google Scholar]
  156. 156.
    Belle NM, Ji Y, Herbine K, Wei Y, Park J et al. 2019. TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths. Nat. Commun. 10:14408
     [Google Scholar]
  157. 157.
    Järvå MA, Lingford JP, John A, Soler NM, Scott NE, Goddard-Borger ED. 2020. Trefoil factors share a lectin activity that defines their role in mucus. Nat. Commun. 11:12265
     [Google Scholar]
  158. 158.
    Goldenring JR, Mills JC. 2022. Cellular plasticity, reprogramming, and regeneration: metaplasia in the stomach and beyond. Gastroenterology 162:2415–30
     [Google Scholar]
  159. 159.
    Petersen CP, Meyer AR, De Salvo C, Choi E, Schlegel C et al. 2018. A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach. Gut 67:5805–17
     [Google Scholar]
  160. 160.
    Noto CN, Hoft SG, Bockerstett KA, Jackson NM, Ford EL et al. 2022. IL13 acts directly on gastric epithelial cells to promote metaplasia development during chronic gastritis. Cell. Mol. Gastroenterol. Hepatol. 13:2623–42
     [Google Scholar]
  161. 161.
    Stanbery AG, Smita S, von Moltke J, Tait Wojno ED, Ziegler SF 2022. TSLP, IL-33, and IL-25: not just for allergy and helminth infection. J. Allergy Clin. Immunol. 150:61302–13
     [Google Scholar]
  162. 162.
    Spits H, Mjösberg J. 2022. Heterogeneity of type 2 innate lymphoid cells. Nat. Rev. Immunol. 22:701–12
     [Google Scholar]
  163. 163.
    Cayrol C, Girard J-P. 2022. Interleukin-33 (IL-33): a critical review of its biology and the mechanisms involved in its release as a potent extracellular cytokine. Cytokine 156:155891
     [Google Scholar]
  164. 164.
    Gause WC, Wynn TA, Allen JE. 2013. Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nat. Rev. Immunol. 13:8607–14
     [Google Scholar]
  165. 165.
    Dwyer GK, D'Cruz LM, Turnquist HR 2022. Emerging functions of IL-33 in homeostasis and immunity. Annu. Rev. Immunol. 40:15–43
     [Google Scholar]
  166. 166.
    Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S et al. 2015. A distinct function of regulatory T cells in tissue protection. Cell 162:51078–89
     [Google Scholar]
  167. 167.
    Muñoz-Rojas AR, Mathis D. 2021. Tissue regulatory T cells: regulatory chameleons. Nat. Rev. Immunol. 21:9597–611
     [Google Scholar]
  168. 168.
    Zaiss DM, Minutti CM, Knipper JA. 2019. Immune- and non-immune-mediated roles of regulatory T-cells during wound healing. Immunology 157:3190–97
     [Google Scholar]
  169. 169.
    Kurowska-Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan CJ et al. 2009. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J. Immunol. 183:106469–77
     [Google Scholar]
  170. 170.
    Zaiss MM, Kurowska-Stolarska M, Böhm C, Gary R, Scholtysek C et al. 2011. IL-33 shifts the balance from osteoclast to alternatively activated macrophage differentiation and protects from TNF-alpha-mediated bone loss. J. Immunol. 186:116097–105
     [Google Scholar]
  171. 171.
    Meyer AR, Engevik AC, Madorsky T, Belmont E, Stier MT et al. 2020. Group 2 innate lymphoid cells coordinate damage response in the stomach. Gastroenterology 159:62077–91.e8
     [Google Scholar]
  172. 172.
    Gadani SP, Smirnov I, Wiltbank AT, Overall CC, Kipnis J. 2017. Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury. J. Exp. Med. 214:2285–96
     [Google Scholar]
  173. 173.
    Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CGK et al. 2011. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 12:111045–54
     [Google Scholar]
  174. 174.
    Rak GD, Osborne LC, Siracusa MC, Kim BS, Wang K et al. 2016. IL-33-dependent group 2 innate lymphoid cells promote cutaneous wound healing. J. Investig. Dermatol. 136:2487–96
     [Google Scholar]
  175. 175.
    Hung L-Y, Lewkowich IP, Dawson LA, Downey J, Yang Y et al. 2013. IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms. PNAS 110:1282–87
     [Google Scholar]
  176. 176.
    Symowski C, Voehringer D. 2019. Th2 cell-derived IL-4/IL-13 promote ILC2 accumulation in the lung by ILC2-intrinsic STAT6 signaling in mice. Eur. J. Immunol. 49:91421–32
     [Google Scholar]
  177. 177.
    Bouchery T, Kyle R, Camberis M, Shepherd A, Filbey K et al. 2015. ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms. Nat. Commun. 6:6970
     [Google Scholar]
  178. 178.
    Ricardo-Gonzalez RR, Kotas ME, O'Leary CE, Singh K, Damsky W et al. 2022. Innate type 2 immunity controls hair follicle commensalism by Demodex mites. 2022. Immunity 55:1891–908.e12
     [Google Scholar]
  179. 179.
    Jarick KJ, Topczewska PM, Jakob MO, Yano H, Arifuzzaman M et al. 2022. Non-redundant functions of group 2 innate lymphoid cells. Nature 611:794–800
     [Google Scholar]
  180. 180.
    Boothby IC, Kinet MJ, Boda DP, Kwan EY, Clancy S et al. 2021. Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin. Nature 599:667–72
     [Google Scholar]
  181. 181.
    Wong VW, Paterno J, Sorkin M, Glotzbach JP, Levi K et al. 2011. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation. FASEB J. 25:124498–510
     [Google Scholar]
  182. 182.
    Liu Q, Dwyer GK, Zhao Y, Li H, Mathews LR et al. 2019. IL-33-mediated IL-13 secretion by ST2+ Tregs controls inflammation after lung injury. JCI Insight. 4:6e123919
     [Google Scholar]
  183. 183.
    Minutti CM, Drube S, Blair N, Schwartz C, McCrae JC et al. 2017. Epidermal growth factor receptor expression licenses type-2 helper T cells to function in a T cell receptor-independent fashion. Immunity 47:4710–22.e6
     [Google Scholar]
  184. 184.
    Ansaldo E, Farley TK, Belkaid Y. 2021. Control of immunity by the microbiota. Annu. Rev. Immunol. 39:449–79
     [Google Scholar]
  185. 185.
    Harrison OJ, Linehan JL, Shih H-Y, Bouladoux N, Han S-J et al. 2019. Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science 363:6422eaat6280
     [Google Scholar]
  186. 186.
    Mukai K, Tsai M, Saito H, Galli SJ. 2018. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol. Rev. 282:1121–50
     [Google Scholar]
  187. 187.
    Finlay CM, Cunningham KT, Doyle B, Mills KHG 2020. IL-33-stimulated murine mast cells polarize alternatively activated macrophages, which suppress T cells that mediate experimental autoimmune encephalomyelitis. J. Immunol. 205:71909–19
     [Google Scholar]
  188. 188.
    Lefrançais E, Duval A, Mirey E, Roga S, Espinosa E et al. 2014. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells. PNAS 111:4315502–7
     [Google Scholar]
  189. 189.
    Peng J, Siracusa MC. 2021. Basophils in antihelminth immunity. Semin. Immunol. 53:101529101529
     [Google Scholar]
  190. 190.
    Sicklinger F, Meyer IS, Li X, Radtke D, Dicks S et al. 2021. Basophils balance healing after myocardial infarction via IL-4/IL-13. J. Clin. Investig. 131:13e136778
     [Google Scholar]
  191. 191.
    Shiraishi M, Shintani Y, Shintani Y, Ishida H, Saba R et al. 2016. Alternatively activated macrophages determine repair of the infarcted adult murine heart. J. Clin. Investig. 126:62151–66
     [Google Scholar]
  192. 192.
    Inclan-Rico JM, Ponessa JJ, Valero-Pacheco N, Hernandez CM, Sy CB et al. 2020. Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition. Nat. Immunol. 21:101181–93
     [Google Scholar]
  193. 193.
    Cohen M, Giladi A, Gorki A-D, Solodkin DG, Zada M et al. 2018. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175:41031–44.e18
     [Google Scholar]
  194. 194.
    Shah K, Ignacio A, McCoy KD, Harris NL. 2020. The emerging roles of eosinophils in mucosal homeostasis. Mucosal Immunol. 13:4574–83
     [Google Scholar]
  195. 195.
    Peiseler M, Kubes P. 2019. More friend than foe: the emerging role of neutrophils in tissue repair. J. Clin. Investig. 129:72629–39
     [Google Scholar]
  196. 196.
    Allen JE, Sutherland TE, Rückerl D. 2015. IL-17 and neutrophils: unexpected players in the type 2 immune response. Curr. Opin. Immunol. 34:99–106
     [Google Scholar]
  197. 197.
    Chen F, Wu W, Millman A, Craft JF, Chen E et al. 2014. Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion. Nat. Immunol. 15:10938–46
     [Google Scholar]
  198. 198.
    Ajendra J, Chenery AL, Parkinson JE, Chan BHK, Pearson S et al. 2020. IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type-2 immune response to nematode infection. Mucosal Immunol 13:958–68
     [Google Scholar]
  199. 199.
    Faas M, Ipseiz N, Ackermann J, Culemann S, Grüneboom A et al. 2021. IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation. Immunity 54:112531–46.e5
     [Google Scholar]
  200. 200.
    Belmesk L, Muntyanu A, Cantin E, AlHalees Z, Jack CS et al. 2022. Prominent role of type 2 immunity in skin diseases: beyond atopic dermatitis. J. Cutan. Med. Surg. 26:133–49
     [Google Scholar]
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IL-4 and IL-13: Regulators and Effectors of Wound Repair
Annual Review of Immunology 41, 229 (2023); https://doi.org/10.1146/annurev-immunol-101921-041206
/content/journals/10.1146/annurev-immunol-101921-041206
/content/journals/10.1146/annurev-immunol-101921-041206
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