1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 40, 2022
  5. Article

Annual Review of Immunology

Volume 40, 2022

Emerging Paradigms in Type 2 Immunity

Abstract

A principal purpose of type 2 immunity was thought to be defense against large parasites, but it also functions in the restoration of homeostasis, such as toxin clearance following snake bites. In other cases, like allergy, the type 2 T helper (Th2) cytokines and cells present in the environment are detrimental and cause diseases. In recent years, the recognition of cell heterogeneity within Th2-associated cell populations has revealed specific functions of cells with a particular phenotype or gene signature. In addition, here we discuss the recent data regarding heterogeneity of type 2 immunity–related cells, as well as their newly identified role in a variety of processes ranging from involvement in respiratory viral infections [especially in the context of the recent COVID-19 (coronavirus disease 2019) pandemic] to control of cancer development or of metabolic homeostasis.

Keyword(s): cancer, metabolism, neuroimmune interactions, respiratory viruses, type 2 immunity
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-101320-030339
2022-04-26
2024-05-08
Loading full text...

Full text loading...

/deliver/fulltext/immunol/40/1/annurev-immunol-101320-030339.html?itemId=/content/journals/10.1146/annurev-immunol-101320-030339&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    El-Naccache DW, Hasko G, Gause WC 2021. Early events triggering the initiation of a type 2 immune response. Trends Immunol 42:151–64
     [Google Scholar]
  2. 2. 
    Starkl P, Gaudenzio N, Marichal T, Reber LL, Sibilano R et al. 2021. IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells. Allergy 77:499–512
     [Google Scholar]
  3. 3. 
    Marichal T, Starkl P, Reber LL, Kalesnikoff J, Oettgen HC et al. 2013. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity 39:963–75
     [Google Scholar]
  4. 4. 
    Bosteels C, Neyt K, Vanheerswynghels M, van Helden MJ, Sichien D et al. 2020. Inflammatory type 2 cDCs acquire features of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity 52:1039–56.e9
     [Google Scholar]
  5. 5. 
    Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I et al. 2014. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40:425–35
     [Google Scholar]
  6. 6. 
    Gowthaman U, Chen JS, Zhang B, Flynn WF, Lu Y et al. 2019. Identification of a T follicular helper cell subset that drives anaphylactic IgE. Science 365:eaaw6433
     [Google Scholar]
  7. 7. 
    Henderson NC, Rieder F, Wynn TA 2020. Fibrosis: from mechanisms to medicines. Nature 587:555–66
     [Google Scholar]
  8. 8. 
    Morimoto Y, Hirahara K, Kiuchi M, Wada T, Ichikawa T et al. 2018. Amphiregulin-producing pathogenic memory T helper 2 cells instruct eosinophils to secrete osteopontin and facilitate airway fibrosis. Immunity 49:134–50.e6
     [Google Scholar]
  9. 9. 
    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:e136778
     [Google Scholar]
  10. 10. 
    Seumois G, Ramirez-Suastegui C, Schmiedel BJ, Liang S, Peters B et al. 2020. Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma. Sci. Immunol. 5:eaba6087
     [Google Scholar]
  11. 11. 
    Tibbitt CA, Stark JM, Martens L, Ma J, Mold JE et al. 2019. Single-cell RNA sequencing of the T helper cell response to house dust mites defines a distinct gene expression signature in airway Th2 cells. Immunity 51:169–84.e5
     [Google Scholar]
  12. 12. 
    Vieira Braga FA, Kar G, Berg M, Carpaij OA, Polanski K et al. 2019. A cellular census of human lungs identifies novel cell states in health and in asthma. Nat. Med. 25:1153–63
     [Google Scholar]
  13. 13. 
    Angkasekwinai P, Dong C. 2021. IL-9-producing T cells: potential players in allergy and cancer. Nat. Rev. Immunol. 21:37–48
     [Google Scholar]
  14. 14. 
    Micosse C, von Meyenn L, Steck O, Kipfer E, Adam C et al. 2019. Human “TH9” cells are a subpopulation of PPAR-γ+ TH2 cells. Sci. Immunol. 4:eaat5943
     [Google Scholar]
  15. 15. 
    Irvin C, Zafar I, Good J, Rollins D, Christianson C et al. 2014. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J. Allergy Clin. Immunol. 134:1175–86.e7
     [Google Scholar]
  16. 16. 
    Hammad H, Lambrecht BN 2021. The basic immunology of asthma. Cell 184:1469–85
     [Google Scholar]
  17. 17. 
    Clement RL, Daccache J, Mohammed MT, Diallo A, Blazar BR et al. 2019. Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses. Nat. Immunol. 20:1360–71
     [Google Scholar]
  18. 18. 
    Canete PF, Sweet RA, Gonzalez-Figueroa P, Papa I, Ohkura N et al. 2019. Regulatory roles of IL-10-producing human follicular T cells. J. Exp. Med. 216:1843–56
     [Google Scholar]
  19. 19. 
    Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K et al. 2014. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513:564–68
     [Google Scholar]
  20. 20. 
    Kolodin D, van Panhuys N, Li C, Magnuson AM, Cipolletta D et al. 2015. Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab 21:543–57
     [Google Scholar]
  21. 21. 
    Faustino LD, Griffith JW, Rahimi RA, Nepal K, Hamilos DL et al. 2020. Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung. Nat. Immunol. 21:1371–83
     [Google Scholar]
  22. 22. 
    Hung L-Y, Tanaka Y, Herbine K, Pastore C, Singh B et al. 2020. Cellular context of IL-33 expression dictates impact on anti-helminth immunity. Sci. Immunol. 5:eabc6259
     [Google Scholar]
  23. 23. 
    Koh B, Ulrich BJ, Nelson AS, Panangipalli G, Kharwadkar R et al. 2020. Bcl6 and Blimp1 reciprocally regulate ST2+ Treg-cell development in the context of allergic airway inflammation. J. Allergy Clin. Immunol. 146:1121–36.e9
     [Google Scholar]
  24. 24. 
    Dahlgren MW, Jones SW, Cautivo KM, Dubinin A, Ortiz-Carpena JF et al. 2019. Adventitial stromal cells define group 2 innate lymphoid cell tissue niches. Immunity 50:707–22.e6
     [Google Scholar]
  25. 25. 
    Ricardo-Gonzalez RR, Van Dyken SJ, Schneider C, Lee J, Nussbaum JC et al. 2018. Tissue signals imprint ILC2 identity with anticipatory function. Nat. Immunol 19:1093–99
     [Google Scholar]
  26. 26. 
    Schneider C, Lee J, Koga S, Ricardo-Gonzalez RR, Nussbaum JC et al. 2019. Tissue-resident group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming. Immunity 50:1425–38.e5
     [Google Scholar]
  27. 27. 
    Flamar AL, Klose CSN, Moeller JB, Mahlakoiv T, Bessman NJ et al. 2020. Interleukin-33 induces the enzyme tryptophan hydroxylase 1 to promote inflammatory group 2 innate lymphoid cell-mediated immunity. Immunity 52:606–19.e6
     [Google Scholar]
  28. 28. 
    Miller MM, Patel PS, Bao K, Danhorn T, O'Connor BP, Reinhardt RL. 2020. BATF acts as an essential regulator of IL-25-responsive migratory ILC2 cell fate and function. Sci. Immunol. 5:eaay3994
     [Google Scholar]
  29. 29. 
    Ricardo-Gonzalez RR, Schneider C, Liao C, Lee J, Liang HE, Locksley RM. 2020. Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity. J. Exp. Med. 217:e20191172
     [Google Scholar]
  30. 30. 
    van der Ploeg EK, Golebski K, van Nimwegen M, Fergusson JR, Heesters BA et al. 2021. Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases. Sci. Immunol. 6:eabd3489
     [Google Scholar]
  31. 31. 
    Golebski K, Layhadi JA, Sahiner U, Steveling-Klein EH, Lenormand MM et al. 2021. Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response. Immunity 54:291–307.e7
     [Google Scholar]
  32. 32. 
    Haim-Vilmovsky L, Henriksson J, Walker JA, Miao Z, Natan E et al. 2021. Mapping Rora expression in resting and activated CD4+ T cells. PLOS ONE 16:e0251233
     [Google Scholar]
  33. 33. 
    Malhotra N, Leyva-Castillo JM, Jadhav U, Barreiro O, Kam C et al. 2018. RORα-expressing T regulatory cells restrain allergic skin inflammation. Sci. Immunol. 3:eaao6923
     [Google Scholar]
  34. 34. 
    Gause WC, Rothlin C, Loke P. 2020. Heterogeneity in the initiation, development and function of type 2 immunity. Nat. Rev. Immunol. 20:603–14
     [Google Scholar]
  35. 35. 
    Jacobsen EA, Jackson DJ, Heffler E, Mathur SK, Bredenoord AJ et al. 2021. Eosinophil knockout humans: uncovering the role of eosinophils through eosinophil-directed biological therapies. Annu. Rev. Immunol. 39:719–57
     [Google Scholar]
  36. 36. 
    Yuan S, Hollinger M, Lachowicz-Scroggins ME, Kerr SC, Dunican EM et al. 2015. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels. Sci. Transl. Med. 7:276ra27
     [Google Scholar]
  37. 37. 
    Persson EK, Verstraete K, Heyndrickx I, Gevaert E, Aegerter H et al. 2019. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science 364:eaaw4295
     [Google Scholar]
  38. 38. 
    Kuo HP, Yu TR, Yu CT 1994. Hypodense eosinophil number relates to clinical severity, airway hyperresponsiveness and response to inhaled corticosteroids in asthmatic subjects. Eur. Respir. J. 7:1452–59
     [Google Scholar]
  39. 39. 
    Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA et al. 2016. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J. Clin. Investig. 126:3279–95
     [Google Scholar]
  40. 40. 
    Stewart E, Wang X, Chupp GL, Montgomery RR. 2020. Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF. J. Leukoc. Biol. 108:1555–64
     [Google Scholar]
  41. 41. 
    Lacy P. 2020. Gr1 makes an unexpected cameo appearance in eosinophils. J. Leukoc. Biol. 107:363–65
     [Google Scholar]
  42. 42. 
    Percopo CM, Brenner TA, Ma M, Kraemer LS, Hakeem RM et al. 2017. SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice. J. Leukoc. Biol. 101:321–28
     [Google Scholar]
  43. 43. 
    Limkar AR, Mai E, Sek AC, Percopo CM, Rosenberg HF. 2020. Frontline Science: Cytokine-mediated developmental phenotype of mouse eosinophils; IL-5-associated expression of the Ly6G/Gr1 surface Ag. J. Leukoc. Biol. 107:367–77
     [Google Scholar]
  44. 44. 
    Jeong BM, Walker MT, Rodriguez R, Coden ME, Nagasaka R et al. 2021. More than neutrophils: Lin+Ly6G+IL-5Rα+ multipotent myeloid cells (MMCs) are dominant in normal murine bone marrow and retain capacity to differentiate into eosinophils and monocytes. J. Leukoc. Biol. 111:113–22
     [Google Scholar]
  45. 45. 
    Berdnikovs S. 2021. The twilight zone: plasticity and mixed ontogeny of neutrophil and eosinophil granulocyte subsets. Semin. Immunopathol. 43:3337–46
     [Google Scholar]
  46. 46. 
    Miyata J, Fukunaga K, Kawashima Y, Watanabe T, Saitoh A et al. 2019. Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis. Allergy 74:1113–24
     [Google Scholar]
  47. 47. 
    Beckert H, Meyer-Martin H, Buhl R, Taube C, Reuter S 2020. Single and synergistic effects of type 2 cytokines on eosinophils and asthma hallmarks. J. Immunol. 204:550–58
     [Google Scholar]
  48. 48. 
    Marichal T, Mesnil C, Bureau F. 2017. Homeostatic eosinophils: characteristics and functions. Front. Med. 4:101
     [Google Scholar]
  49. 49. 
    Yun Y, Kanda A, Kobayashi Y, Van Bui D, Suzuki K et al. 2020. Increased CD69 expression on activated eosinophils in eosinophilic chronic rhinosinusitis correlates with clinical findings. Allergol. Int. 69:232–38
     [Google Scholar]
  50. 50. 
    Doan TC, Jeong BM, Coden ME, Loffredo LF, Bhattacharyya S et al. 2018. Matrix protein tenascin-C expands and reversibly blocks maturation of murine eosinophil progenitors. J. Allergy Clin. Immunol. 142:695–98.e4
     [Google Scholar]
  51. 51. 
    Kelly EA, Esnault S, Liu LY, Evans MD, Johansson MW et al. 2017. Mepolizumab attenuates airway eosinophil numbers, but not their functional phenotype, in asthma. Am. J. Respir. Crit. Care Med. 196:1385–95
     [Google Scholar]
  52. 52. 
    Medzhitov R, Schneider DS, Soares MP. 2012. Disease tolerance as a defense strategy. Science 335:936–41
     [Google Scholar]
  53. 53. 
    Kabata H, Artis D. 2019. Neuro-immune crosstalk and allergic inflammation. J. Clin. Investig. 129:1475–82
     [Google Scholar]
  54. 54. 
    Chesne J, Cardoso V, Veiga-Fernandes H. 2019. Neuro-immune regulation of mucosal physiology. Mucosal Immunol 12:10–20
     [Google Scholar]
  55. 55. 
    Wang W, Seale P 2016. Control of brown and beige fat development. Nat. Rev. Mol. Cell Biol. 17:691–702
     [Google Scholar]
  56. 56. 
    Roberts LB, Schnoeller C, Berkachy R, Darby M, Pillaye J et al. 2021. Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths. Sci. Immunol. 6:eabd0359
     [Google Scholar]
  57. 57. 
    Chu C, Parkhurst CN, Zhang W, Zhou L, Yano H et al. 2021. The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity. Sci. Immunol. 6:eabe3218
     [Google Scholar]
  58. 58. 
    Klose CSN, Mahlakoiv T, Moeller JB, Rankin LC, Flamar AL et al. 2017. The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature 549:282–86
     [Google Scholar]
  59. 59. 
    Cardoso V, Chesne J, Ribeiro H, Garcia-Cassani B, Carvalho T et al. 2017. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature 549:277–81
     [Google Scholar]
  60. 60. 
    Wallrapp A, Riesenfeld SJ, Burkett PR, Abdulnour RE, Nyman J et al. 2017. The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature 549:351–56. Erratum. 2017. Nature 551:658
     [Google Scholar]
  61. 61. 
    Nagashima H, Mahlakoiv T, Shih HY, Davis FP, Meylan F et al. 2019. Neuropeptide CGRP limits group 2 innate lymphoid cell responses and constrains type 2 inflammation. Immunity 51:682–95.e6
     [Google Scholar]
  62. 62. 
    Perner C, Flayer CH, Zhu X, Aderhold PA, Dewan ZNA et al. 2020. Substance P release by sensory neurons triggers dendritic cell migration and initiates the type-2 immune response to allergens. Immunity 53:1063–77.e7
     [Google Scholar]
  63. 63. 
    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. 21:1181–93
     [Google Scholar]
  64. 64. 
    Ural BB, Yeung ST, Damani-Yokota P, Devlin JC, de Vries M et al. 2020. Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties. Sci. Immunol. 5:eaax8756
     [Google Scholar]
  65. 65. 
    Lambrecht BN. 2001. Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation. Respir. Res. 2:133–38
     [Google Scholar]
  66. 66. 
    Veiga-Fernandes H, Pachnis V. 2017. Neuroimmune regulation during intestinal development and homeostasis. Nat. Immunol. 18:116–22
     [Google Scholar]
  67. 67. 
    Veiga-Fernandes H, Artis D. 2018. Neuronal-immune system cross-talk in homeostasis. Science 359:1465–66
     [Google Scholar]
  68. 68. 
    Feddema JJ, Claassen E. 2020. Prevalence of viral respiratory infections amongst asthmatics: results of a meta-regression analysis. Respir. Med. 173:106020
     [Google Scholar]
  69. 69. 
    Hansel TT, Tunstall T, Trujillo-Torralbo MB, Shamji B, Del-Rosario A et al. 2017. A comprehensive evaluation of nasal and bronchial cytokines and chemokines following experimental rhinovirus infection in allergic asthma: increased interferons (IFN-γ and IFN-λ) and type 2 inflammation (IL-5 and IL-13). EBioMedicine 19:128–38
     [Google Scholar]
  70. 70. 
    Zhu J, Message SD, Mallia P, Kebadze T, Contoli M et al. 2019. Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations. J. Allergy Clin. Immunol. 143:114–25.e4
     [Google Scholar]
  71. 71. 
    Gill MA, Bajwa G, George TA, Dong CC, Dougherty II et al. 2010. Counterregulation between the FcεRI pathway and antiviral responses in human plasmacytoid dendritic cells. J. Immunol. 184:5999–6006
     [Google Scholar]
  72. 72. 
    Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD et al. 2020. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—an update on the status. Mil. Med. Res. 7:11
     [Google Scholar]
  73. 73. 
    Kalfaoglu B, Almeida-Santos J, Tye CA, Satou Y, Ono M. 2020. T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis. Front. Immunol. 11:589380
     [Google Scholar]
  74. 74. 
    Weiskopf D, Schmitz KS, Raadsen MP, Grifoni A, Okba NMA et al. 2020. Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci. Immunol. 5:eabd2071
     [Google Scholar]
  75. 75. 
    Xiong Y, Liu Y, Cao L, Wang D, Guo M et al. 2020. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg. Microbes Infect. 9:761–70
     [Google Scholar]
  76. 76. 
    Tan M, Liu Y, Zhou R, Deng X, Li F et al. 2020. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. Immunology 160:261–68
     [Google Scholar]
  77. 77. 
    Schuijs MJ, Png S, Richard AC, Tsyben A, Hamm G et al. 2020. ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung. Nat. Immunol. 21:998–1009
     [Google Scholar]
  78. 78. 
    Lynch JP, Werder RB, Simpson J, Loh Z, Zhang V et al. 2016. Aeroallergen-induced IL-33 predisposes to respiratory virus-induced asthma by dampening antiviral immunity. J Allergy Clin. Immunol. 138:1326–37
     [Google Scholar]
  79. 79. 
    Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L et al. 2020. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 323:1574–81
     [Google Scholar]
  80. 80. 
    Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS et al. 2020. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur. Respir. J. 55:2000547
     [Google Scholar]
  81. 81. 
    Hanon S, Brusselle G, Deschampheleire M, Louis R, Michils A et al. 2020. COVID-19 and biologics in severe asthma: data from the Belgian Severe Asthma Registry. Eur. Respir. J. 56:62002857
     [Google Scholar]
  82. 82. 
    Kimura H, Francisco D, Conway M, Martinez FD, Vercelli D et al. 2020. Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells. J. Allergy Clin. Immunol. 146:80–88.e8
     [Google Scholar]
  83. 83. 
    Sajuthi SP, DeFord P, Li Y, Jackson ND, Montgomery MT et al. 2020. Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. Nat. Commun. 11:5139
     [Google Scholar]
  84. 84. 
    Peters MC, Sajuthi S, Deford P, Christenson S, Rios CL et al. 2020. COVID-19-related genes in sputum cells in asthma: relationship to demographic features and corticosteroids. Am. J. Respir. Crit. Care Med. 202:83–90
     [Google Scholar]
  85. 85. 
    WHO Rapid Evid. Apprais. COVID-19 Ther. (REACT) Work. Group 2020. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 3241330–41
  86. 86. 
    Ramakrishnan S, Russell R 2020. In the race at last: post-hoc analysis of GALATHEA and TERRANOVA. Lancet Respir. Med. 8:127–29
     [Google Scholar]
  87. 87. 
    Yang J, Zheng Y, Gou X, Pu K, Chen Z et al. 2020. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int. J. Infect. Dis. 94:91–95
     [Google Scholar]
  88. 88. 
    Donlan AN, Sutherland TE, Marie C, Preissner S, Bradley BT et al. 2021. IL-13 is a driver of COVID-19 severity. JCI Insight 6:15e150107
     [Google Scholar]
  89. 89. 
    Napolitano M, Patruno C, Ruggiero A, Nocerino M, Fabbrocini G. 2020. Safety of dupilumab in atopic patients during COVID-19 outbreak. J. Dermatolog. Treat. 33:600–1
     [Google Scholar]
  90. 90. 
    Patruno C, Stingeni L, Fabbrocini G, Hansel K, Napolitano M. 2020. Dupilumab and COVID-19: What should we expect?. Dermatolog. Ther. 33:e13502
     [Google Scholar]
  91. 91. 
    Bhalla A, Mukherjee M, Radford K, Nazy I, Kjarsgaard M et al. 2021. Dupilumab, severe asthma airway responses, and SARS-CoV-2 serology. Allergy 76:957–58
     [Google Scholar]
  92. 92. 
    Busse WW, Bleecker ER, FitzGerald JM, Ferguson GT, Barker P et al. 2019. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir. Med. 7:46–59
     [Google Scholar]
  93. 93. 
    Jackson DJ, Busse WW, Bacharier LB, Kattan M, O'Connor GT et al. 2020. Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2. J. Allergy Clin. Immunol. 146:203–6.e3
     [Google Scholar]
  94. 94. 
    Samarasinghe AE, Melo RC, Duan S, LeMessurier KS, Liedmann S et al. 2017. Eosinophils promote antiviral immunity in mice infected with influenza A virus. J. Immunol. 198:3214–26
     [Google Scholar]
  95. 95. 
    Lucas C, Wong P, Klein J, Castro TBR, Silva J et al. 2020. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584:463–69
     [Google Scholar]
  96. 96. 
    Liao D, Zhou F, Luo L, Xu M, Wang H et al. 2020. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol 7:e671–78
     [Google Scholar]
  97. 97. 
    Qin C, Zhou L, Hu Z, Zhang S, Yang S et al. 2020. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin. Infect. Dis. 71:762–68
     [Google Scholar]
  98. 98. 
    Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB et al. 2020. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 75:1730–41
     [Google Scholar]
  99. 99. 
    Gebremeskel S, Schanin J, Coyle KM, Butuci M, Luu T et al. 2021. Mast cell and eosinophil activation are associated with COVID-19 and TLR-mediated viral inflammation: implications for an anti-Siglec-8 antibody. Front. Immunol. 12:650331
     [Google Scholar]
  100. 100. 
    Aksu K, Yesilkaya S, Topel M, Turkyilmaz S, Ercelebi DC et al. 2021. COVID-19 in a patient with severe asthma using mepolizumab. Allergy Asthma Proc 42:e55–57
     [Google Scholar]
  101. 101. 
    Chun HJ, Coutavas E, Pine A, Lee AI, Yu V et al. 2021. Immuno-fibrotic drivers of impaired lung function in post-COVID-19 syndrome. medRxiv 2021.01.31.21250870. https://doi.org/10.1101/2021.01.31.21250870
    [Crossref]
  102. 102. 
    Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. 2018. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir. Res. 19:32
     [Google Scholar]
  103. 103. 
    Fabbri L, Jones S. 2021. Changing priorities for pulmonary fibrosis: The patient will see you now. ! Thorax 76:534–35
     [Google Scholar]
  104. 104. 
    Murray LA, Argentieri RL, Farrell FX, Bracht M, Sheng H et al. 2008. Hyper-responsiveness of IPF/UIP fibroblasts: interplay between TGFβ1, IL-13 and CCL2. Int. J. Biochem. Cell Biol. 40:2174–82
     [Google Scholar]
  105. 105. 
    Murray LA, Zhang H, Oak SR, Coelho AL, Herath A et al. 2014. Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model. Am. J. Respir. Cell Mol. Biol. 50:985–94
     [Google Scholar]
  106. 106. 
    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. 239:344–54
     [Google Scholar]
  107. 107. 
    Casanova-Acebes M, Dalla E, Leader AM, LeBerichel J, Nikolic J et al. 2021. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells. Nature 595:7868578–84
     [Google Scholar]
  108. 108. 
    Petty AJ, Li A, Wang X, Dai R, Heyman B et al. 2019. Hedgehog signaling promotes tumor-associated macrophage polarization to suppress intratumoral CD8+ T cell recruitment. J. Clin. Investig. 129:5151–62
     [Google Scholar]
  109. 109. 
    Tan IL, Arifa RDN, Rallapalli H, Kana V, Lao Z et al. 2021. CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic hedgehog-medulloblastoma model. Oncogene 40:396–407
     [Google Scholar]
  110. 110. 
    Yang JB, Zhao ZB, Liu QZ, Hu TD, Long J et al. 2018. FoxO1 is a regulator of MHC-II expression and anti-tumor effect of tumor-associated macrophages. Oncogene 37:1192–204
     [Google Scholar]
  111. 111. 
    Zhu P, Zhu X, Wu J, He L, Lu T et al. 2019. IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat. Immunol. 20:183–94
     [Google Scholar]
  112. 112. 
    Matsui S, Okabayashi K, Tsuruta M, Shigeta K, Seishima R et al. 2019. Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis. Cancer Sci 110:2156–65
     [Google Scholar]
  113. 113. 
    Wu Y, Konate MM, Lu J, Makhlouf H, Chuaqui R et al. 2019. IL-4 and IL-17A cooperatively promote hydrogen peroxide production, oxidative DNA damage, and upregulation of dual oxidase 2 in human colon and pancreatic cancer cells. J. Immunol. 203:2532–44
     [Google Scholar]
  114. 114. 
    Maier B, Leader AM, Chen ST, Tung N, Chang C et al. 2020. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580:257–62
     [Google Scholar]
  115. 115. 
    Liu M, Kuo F, Capistrano KJ, Kang D, Nixon BG et al. 2020. TGF-β suppresses type 2 immunity to cancer. Nature 587:115–20
     [Google Scholar]
  116. 116. 
    Nakamura M, Souri EA, Osborn G, Laddach R, Chauhan J et al. 2020. IgE activates monocytes from cancer patients to acquire a pro-inflammatory phenotype. Cancers 12:3376
     [Google Scholar]
  117. 117. 
    Protti MP, De Monte L. 2020. Thymic stromal lymphopoietin and cancer: Th2-dependent and -independent mechanisms. Front. Immunol. 11:2088
     [Google Scholar]
  118. 118. 
    Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E et al. 2021. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N. Engl. J. Med. 384:1800–9
     [Google Scholar]
  119. 119. 
    Lucarini V, Ziccheddu G, Macchia I, La Sorsa V, Peschiaroli F et al. 2017. IL-33 restricts tumor growth and inhibits pulmonary metastasis in melanoma-bearing mice through eosinophils. OncoImmunology 6:e1317420
     [Google Scholar]
  120. 120. 
    Gao X, Wang X, Yang Q, Zhao X, Wen W et al. 2015. Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells. J. Immunol. 194:438–45
     [Google Scholar]
  121. 121. 
    Hatzioannou A, Banos A, Sakelaropoulos T, Fedonidis C, Vidali MS et al. 2020. An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion. Nat. Immunol. 21:75–85
     [Google Scholar]
  122. 122. 
    Ameri AH, Moradi Tuchayi S, Zaalberg A, Park JH, Ngo KH et al. 2019. IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation. PNAS 116:2646–51
     [Google Scholar]
  123. 123. 
    Taniguchi S, Elhance A, Van Duzer A, Kumar S, Leitenberger JJ, Oshimori N 2020. Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression. Science 369:eaay1813
     [Google Scholar]
  124. 124. 
    Salimi M, Wang R, Yao X, Li X, Wang X et al. 2018. Activated innate lymphoid cell populations accumulate in human tumour tissues. BMC Cancer 18:341
     [Google Scholar]
  125. 125. 
    Loyon R, Jary M, Salome B, Gomez-Cadena A, Galaine J et al. 2019. Peripheral innate lymphoid cells are increased in first line metastatic colorectal carcinoma patients: a negative correlation with Th1 immune responses. Front. Immunol. 10:2121
     [Google Scholar]
  126. 126. 
    Trabanelli S, Chevalier MF, Martinez-Usatorre A, Gomez-Cadena A, Salome B et al. 2017. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nat. Commun. 8:593
     [Google Scholar]
  127. 127. 
    Ercolano G, Gomez-Cadena A, Dumauthioz N, Vanoni G, Kreutzfeldt M et al. 2021. PPAR drives IL-33-dependent ILC2 pro-tumoral functions. Nat. Commun. 12:2538
     [Google Scholar]
  128. 128. 
    Chen T, Tibbitt CA, Feng X, Stark JM, Rohrbeck L et al. 2017. PPAR-gamma promotes type 2 immune responses in allergy and nematode infection. Sci. Immunol. 2:eaal5196
     [Google Scholar]
  129. 129. 
    Rigas D, Lewis G, Aron JL, Wang B, Banie H et al. 2017. Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction. J. Allergy Clin. Immunol. 139:1468–77.e2
     [Google Scholar]
  130. 130. 
    Wan J, Wu Y, Huang L, Tian Y, Ji X et al. 2021. ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8+ T cells. Cancer Lett 502:34–43
     [Google Scholar]
  131. 131. 
    Lotfi R, Lee JJ, Lotze MT. 2007. Eosinophilic granulocytes and damage-associated molecular pattern molecules (DAMPs): role in the inflammatory response within tumors. J. Immunother. 30:16–28
     [Google Scholar]
  132. 132. 
    Varricchi G, Loffredo S, Galdiero MR, Marone G, Cristinziano L et al. 2018. Innate effector cells in angiogenesis and lymphangiogenesis. Curr. Opin. Immunol. 53:152–60
     [Google Scholar]
  133. 133. 
    Hollande C, Boussier J, Ziai J, Nozawa T, Bondet V et al. 2019. Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth. Nat. Immunol. 20:257–64
     [Google Scholar]
  134. 134. 
    Reichman H, Itan M, Rozenberg P, Yarmolovski T, Brazowski E et al. 2019. Activated eosinophils exert antitumorigenic activities in colorectal cancer. Cancer Immunol. Res. 7:388–400
     [Google Scholar]
  135. 135. 
    Arnold IC, Artola-Boran M, Gurtner A, Bertram K, Bauer M et al. 2020. The GM-CSF-IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses. J. Exp. Med. 217:e20190706
     [Google Scholar]
  136. 136. 
    Andreone S, Spadaro F, Buccione C, Mancini J, Tinari A et al. 2019. IL-33 promotes CD11b/CD18-mediated adhesion of eosinophils to cancer cells and synapse-polarized degranulation leading to tumor cell killing. Cancers 11:1664
     [Google Scholar]
  137. 137. 
    Busse WW, Bleecker ER, FitzGerald JM, Ferguson GT, Barker P et al. 2021. Benralizumab for adolescent patients with severe, eosinophilic asthma: safety and efficacy after 3 years of treatment. J. Allergy Clin. Immunol. 148:266–71.e2
     [Google Scholar]
  138. 138. 
    Shikotra A, Ohri CM, Green RH, Waller DA, Bradding P. 2016. Mast cell phenotype, TNF expression and degranulation status in non-small cell lung cancer. Sci. Rep. 6:38352
     [Google Scholar]
  139. 139. 
    Glajcar A, Szpor J, Pacek A, Tyrak KE, Chan F et al. 2017. The relationship between breast cancer molecular subtypes and mast cell populations in tumor microenvironment. Virchows Arch 470:505–15
     [Google Scholar]
  140. 140. 
    Porcelli L, Iacobazzi RM, Di Fonte R, Serrati S, Intini A et al. 2019. CAFs and TGF-β signaling activation by mast cells contribute to resistance to gemcitabine/nabpaclitaxel in pancreatic cancer. Cancers 11:330
     [Google Scholar]
  141. 141. 
    Siebenhaar F, Metz M, Maurer M. 2014. Mast cells protect from skin tumor development and limit tumor growth during cutaneous de novo carcinogenesis in a Kit-dependent mouse model. Exp. Dermatolog. 23:159–64
     [Google Scholar]
  142. 142. 
    Oldford SA, Haidl ID, Howatt MA, Leiva CA, Johnston B, Marshall JS 2010. A critical role for mast cells and mast cell-derived IL-6 in TLR2-mediated inhibition of tumor growth. J. Immunol. 185:7067–76
     [Google Scholar]
  143. 143. 
    Lv Y, Zhao Y, Wang X, Chen N, Mao F et al. 2019. Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-alpha-PD-L1 pathway. J. Immunother. Cancer 7:54
     [Google Scholar]
  144. 144. 
    Keser SH, Kandemir NO, Ece D, Gecmen GG, Gul AE et al. 2017. Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma. Kaohsiung J. Med. Sci. 33:171–80
     [Google Scholar]
  145. 145. 
    Kabiraj A, Jaiswal R, Singh A, Gupta J, Singh A, Samadi FM. 2018. Immunohistochemical evaluation of tumor angiogenesis and the role of mast cells in oral squamous cell carcinoma. J. Cancer Res. Ther. 14:495–502
     [Google Scholar]
  146. 146. 
    Gonzalez-Muniesa P, Martinez-Gonzalez MA, Hu FB, Despres JP, Matsuzawa Y et al. 2017. Obesity.. Nat. Rev. Dis. Primers 3:17034
     [Google Scholar]
  147. 147. 
    Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V et al. 2007. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 447:1116–20
     [Google Scholar]
  148. 148. 
    Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA et al. 2011. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–47
     [Google Scholar]
  149. 149. 
    Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE et al. 2013. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J. Exp. Med. 210:535–49
     [Google Scholar]
  150. 150. 
    Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R et al. 2015. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat. Immunol. 16:276–85
     [Google Scholar]
  151. 151. 
    Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B et al. 2019. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178:686–98.e14
     [Google Scholar]
  152. 152. 
    Spallanzani RG, Zemmour D, Xiao T, Jayewickreme T, Li C et al. 2019. Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci. Immunol. 4:eaaw3658
     [Google Scholar]
  153. 153. 
    Mahlakoiv T, Flamar AL, Johnston LK, Moriyama S, Putzel GG et al. 2019. Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33. Sci. Immunol. 4:eaax0416
     [Google Scholar]
  154. 154. 
    Rana BMJ, Jou E, Barlow JL, Rodriguez-Rodriguez N, Walker JA et al. 2019. A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue. J. Exp. Med. 216:1999–2009
     [Google Scholar]
  155. 155. 
    McLaughlin T, Ackerman SE, Shen L, Engleman E. 2017. Role of innate and adaptive immunity in obesity-associated metabolic disease. J. Clin. Investig. 127:5–13
     [Google Scholar]
  156. 156. 
    Penkov S, Mitroulis I, Hajishengallis G, Chavakis T. 2019. Immunometabolic crosstalk: an ancestral principle of trained immunity?. Trends Immunol 40:1–11
     [Google Scholar]
  157. 157. 
    Christ A, Gunther P, Lauterbach MAR, Duewell P, Biswas D et al. 2018. Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172:162–75.e14
     [Google Scholar]
  158. 158. 
    Fischer IP, Irmler M, Meyer CW, Sachs SJ, Neff F et al. 2018. A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue. Int. J. Obes. 42:507–17
     [Google Scholar]
  159. 159. 
    Chiappetta S, Sharma AM, Bottino V, Stier C. 2020. COVID-19 and the role of chronic inflammation in patients with obesity. Int. J. Obes. 44:1790–92
     [Google Scholar]
  160. 160. 
    Huang Y, Lu Y, Huang YM, Wang M, Ling W et al. 2020. Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabolism 113:154378
     [Google Scholar]
  161. 161. 
    Rogliani P, Sforza M, Calzetta L. 2020. The impact of comorbidities on severe asthma. Curr. Opin. Pulm. Med. 26:47–55
     [Google Scholar]
  162. 162. 
    Brightling CE, Tobin AB, Milligan G. 2019. Fatty airways: a source of good and bad fats?. Eur. Respir. J. 54:1902060
     [Google Scholar]
  163. 163. 
    Elliot JG, Donovan GM, Wang KCW, Green FHY, James AL, Noble PB 2019. Fatty airways: implications for obstructive disease. Eur. Respir. J. 54:1900857
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-101320-030339
Loading
Emerging Paradigms in Type 2 Immunity
Annual Review of Immunology 40, 443 (2022); https://doi.org/10.1146/annurev-immunol-101320-030339
/content/journals/10.1146/annurev-immunol-101320-030339
/content/journals/10.1146/annurev-immunol-101320-030339
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error