1932

Abstract

Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate , they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.

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2020-04-26
2024-10-10
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Literature Cited

  1. 1. 
    Kitamura Y. 1989. Heterogeneity of mast cells and phenotypic change between subpopulations. Annu. Rev. Immunol. 7:59–76
    [Google Scholar]
  2. 2. 
    Galli SJ, Grimbaldeston M, Tsai M 2008. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat. Rev. Immunol. 8:478–86
    [Google Scholar]
  3. 3. 
    Gurish MF, Austen KF. 2012. Developmental origin and functional specialization of mast cell subsets. Immunity 37:25–33
    [Google Scholar]
  4. 4. 
    Dahlin JS, Hallgren J. 2015. Mast cell progenitors: origin, development and migration to tissues. Mol. Immunol. 63:9–17
    [Google Scholar]
  5. 5. 
    Grootens J, Ungerstedt JS, Nilsson G, Dahlin JS 2018. Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells. Blood Adv 2:2273–81
    [Google Scholar]
  6. 6. 
    Metcalfe DD, Baram D, Mekori YA 1997. Mast cells. Physiol. Rev. 77:1033–79
    [Google Scholar]
  7. 7. 
    Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M 2005. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol. 23:749–86
    [Google Scholar]
  8. 8. 
    Bandeira-Melo C, Calheiros AS, Silva PM, Cordeiro RS, Teixeira MM, Martins MA 1999. Suppressive effect of distinct bradykinin B2 receptor antagonist on allergen-evoked exudation and leukocyte infiltration in sensitized rats. Br. J. Pharmacol. 127:315–20
    [Google Scholar]
  9. 9. 
    Jamur MC, Moreno AN, Mello LF, Souza DA Jr., Campos MR et al. 2010. Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors. BMC Immunol 11:32
    [Google Scholar]
  10. 10. 
    Sonoda T, Hayashi C, Kitamura Y 1983. Presence of mast cell precursors in the yolk sac of mice. Dev. Biol. 97:89–94
    [Google Scholar]
  11. 11. 
    Li Z, Liu S, Xu J, Zhang X, Han D et al. 2018. Adult connective tissue-resident mast cells originate from late erythro-myeloid progenitors. Immunity 49:640–53.e5
    [Google Scholar]
  12. 12. 
    Gentek R, Ghigo C, Hoeffel G, Bulle MJ, Msallam R et al. 2018. Hemogenic endothelial fate mapping reveals dual developmental origin of mast cells. Immunity 48:1160–71.e5
    [Google Scholar]
  13. 13. 
    Nilsson G, Dahlin JS. 2019. New insights into the origin of mast cells. Allergy 74:844–45
    [Google Scholar]
  14. 14. 
    Enerbäck L. 1986. Mast cell heterogeneity: the evolution of the concept of a specific mucosal mast cell. Mast Cell Differentiation and Heterogeneity AD Befus, J Bienenstock, JA Denburg 1–26 New York: Raven
    [Google Scholar]
  15. 15. 
    Katz HR, Stevens RL, Austen KF 1985. Heterogeneity of mammalian mast cells differentiated in vivo and in vitro. J. Allergy Clin. Immunol. 76:250–59
    [Google Scholar]
  16. 16. 
    Stevens RL, Austen KF. 1989. Recent advances in the cellular and molecular biology of mast cells. Immunol. Today 10:381–86
    [Google Scholar]
  17. 17. 
    Friend DS, Ghildyal N, Austen KF, Gurish MF, Matsumoto R, Stevens RL 1996. Mast cells that reside at different locations in the jejunum of mice infected with Trichinella spiralis exhibit sequential changes in their granule ultrastructure and chymase phenotype. J. Cell Biol. 135:279–90
    [Google Scholar]
  18. 18. 
    Shimokawa C, Kanaya T, Hachisuka M, Ishiwata K, Hisaeda H et al. 2017. Mast cells are crucial for induction of group 2 innate lymphoid cells and clearance of helminth infections. Immunity 46:863–74.e4
    [Google Scholar]
  19. 19. 
    Irani AM, Schwartz LB. 1994. Human mast cell heterogeneity. Allergy Proc 15:303–8
    [Google Scholar]
  20. 20. 
    Strobel S, Busuttil A, Ferguson A 1983. Human intestinal mucosal mast cells: expanded population in untreated coeliac disease. Gut 24:222–27
    [Google Scholar]
  21. 21. 
    Dwyer DF, Barrett NA, Austen KFImmunol. Genome Proj. Consort 2016. Expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat. Immunol. 17:878–87
    [Google Scholar]
  22. 22. 
    Friend DS, Ghildyal N, Gurish MF, Hunt J, Hu X et al. 1998. Reversible expression of tryptases and chymases in the jejunal mast cells of mice infected with Trichinella spiralis. J. Immunol 160:5537–45
    [Google Scholar]
  23. 23. 
    Cavalcante MC, Allodi S, Valente AP, Straus AH, Takahashi HK et al. 2000. Occurrence of heparin in the invertebrate Styela plicata (Tunicata) is restricted to cell layers facing the outside environment: an ancient role in defense?. J. Biol. Chem. 275:36189–96
    [Google Scholar]
  24. 24. 
    Cavalcante MC, de Andrade LR, Du Bocage Santos-Pinto C, Straus AH, Takahashi HK et al. 2002. Colocalization of heparin and histamine in the intracellular granules of test cells from the invertebrate Styela plicata (Chordata-Tunicata). J. Struct. Biol. 137:313–21
    [Google Scholar]
  25. 25. 
    Crivellato E, Ribatti D. 2010. The mast cell: an evolutionary perspective. Biol. Rev. Camb. Philos. Soc. 85:347–60
    [Google Scholar]
  26. 26. 
    Baccari GC, Pinelli C, Santillo A, Minucci S, Rastogi RK 2011. Mast cells in nonmammalian vertebrates: an overview. Int. Rev. Cell Mol. Biol. 290:1–53
    [Google Scholar]
  27. 27. 
    Wong GW, Zhuo L, Kimata K, Lam BK, Satoh N, Stevens RL 2014. Ancient origin of mast cells. Biochem. Biophys. Res. Commun. 451:314–18
    [Google Scholar]
  28. 28. 
    Hellman LT, Akula S, Thorpe M, Fu Z 2017. Tracing the origins of IgE, mast cells, and allergies by studies of wild animals. Front. Immunol. 8:1749
    [Google Scholar]
  29. 29. 
    Beutier H, Gillis CM, Iannascoli B, Godon O, England P et al. 2017. IgG subclasses determine pathways of anaphylaxis in mice. J. Allergy Clin. Immunol. 139:269–80.e7
    [Google Scholar]
  30. 30. 
    Reber LL, Hernandez JD, Galli SJ 2017. The pathophysiology of anaphylaxis. J. Allergy Clin. Immunol. 140:335–48
    [Google Scholar]
  31. 31. 
    Okayama Y, Kirshenbaum AS, Metcalfe DD 2000. Expression of a functional high-affinity IgG receptor, FcγRI, on human mast cells: up-regulation by IFN-γ. J. Immunol. 164:4332–39
    [Google Scholar]
  32. 32. 
    Woolhiser MR, Okayama Y, Gilfillan AM, Metcalfe DD 2001. IgG-dependent activation of human mast cells following up-regulation of FcγRI by IFN-γ. Eur. J. Immunol. 31:3298–307
    [Google Scholar]
  33. 33. 
    Jonsson F, Mancardi DA, Zhao W, Kita Y, Iannascoli B et al. 2012. Human FcγRIIA induces anaphylactic and allergic reactions. Blood 119:2533–44
    [Google Scholar]
  34. 34. 
    Finkelman FD, Khodoun MV, Strait R 2016. Human IgE-independent systemic anaphylaxis. J. Allergy Clin. Immunol. 137:1674–80
    [Google Scholar]
  35. 35. 
    Malbec O, Daeron M. 2007. The mast cell IgG receptors and their roles in tissue inflammation. Immunol. Rev. 217:206–21
    [Google Scholar]
  36. 36. 
    Jonsson F, Daeron M. 2012. Mast cells and company. Front. Immunol. 3:16
    [Google Scholar]
  37. 37. 
    Ali H. 2010. Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunol. Lett. 128:36–45
    [Google Scholar]
  38. 38. 
    Schafer B, Piliponsky AM, Oka T, Song CH, Gerard NP et al. 2013. Mast cell anaphylatoxin receptor expression can enhance IgE-dependent skin inflammation in mice. J. Allergy Clin. Immunol. 131:541–48
    [Google Scholar]
  39. 39. 
    Marshall JS. 2004. Mast-cell responses to pathogens. Nat. Rev. Immunol. 4:787–99
    [Google Scholar]
  40. 40. 
    Abraham SN St, John AL 2010. Mast cell-orchestrated immunity to pathogens. Nat. Rev. Immunol. 10:440–52
    [Google Scholar]
  41. 41. 
    Redegeld FA, Yu Y, Kumari S, Charles N, Blank U 2018. Non-IgE mediated mast cell activation. Immunol. Rev. 282:87–113
    [Google Scholar]
  42. 42. 
    Rudich N, Ravid K, Sagi-Eisenberg R 2012. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation. Front. Immunol. 3:134
    [Google Scholar]
  43. 43. 
    Galli SJ, Tsai M, Wershil BK 1993. The c-kit receptor, stem cell factor, and mast cells: what each is teaching us about the others. Am. J. Pathol. 142:965–74
    [Google Scholar]
  44. 44. 
    Lennartsson J, Ronnstrand L. 2012. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol. Rev. 92:1619–49
    [Google Scholar]
  45. 45. 
    Yano H, Wershil BK, Arizono N, Galli SJ 1989. Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent. J. Clin. Investig. 84:1276–86
    [Google Scholar]
  46. 46. 
    Kulka M, Sheen CH, Tancowny BP, Grammer LC, Schleimer RP 2008. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology 123:398–410
    [Google Scholar]
  47. 47. 
    Gaudenzio N, Sibilano R, Marichal T, Starkl P, Reber LL et al. 2016. Different activation signals induce distinct mast cell degranulation strategies. J. Clin. Investig. 126:3981–98
    [Google Scholar]
  48. 48. 
    Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A et al. 2011. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. J. Clin. Investig. 121:4180–91
    [Google Scholar]
  49. 49. 
    Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M et al. 2006. Mast cells can enhance resistance to snake and honeybee venoms. Science 313:526–30
    [Google Scholar]
  50. 50. 
    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]
  51. 51. 
    Starkl P, Marichal T, Gaudenzio N, Reber LL, Sibilano R et al. 2016. IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity. J. Allergy Clin. Immunol. 137:246–57.e11
    [Google Scholar]
  52. 52. 
    Voehringer D. 2013. Protective and pathological roles of mast cells and basophils. Nat. Rev. Immunol. 13:362–75
    [Google Scholar]
  53. 53. 
    Marone G, Borriello F, Varricchi G, Genovese A, Granata F 2014. Basophils: historical reflections and perspectives. Chem. Immunol. Allergy 100:172–92
    [Google Scholar]
  54. 54. 
    Galli SJ, Metcalfe DD, Arber DA, Dvorak AM 2015. Basophils, mast cells, and related disorders. Williams Hematology K Kaushansky, MA Lichtman, E Beutler, TJ Kipps, JT Prchal 965–81 New York: McGraw-Hill Medical
    [Google Scholar]
  55. 55. 
    Varricchi G, Raap U, Rivellese F, Marone G, Gibbs BF 2018. Human mast cells and basophils—How are they similar how are they different?. Immunol. Rev. 282:8–34
    [Google Scholar]
  56. 56. 
    Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y 2018. Multifaceted roles of basophils in health and disease. J. Allergy Clin. Immunol. 142:370–80
    [Google Scholar]
  57. 57. 
    Piliponsky AM, Shubin NJ, Lahiri AK, Truong P, Clauson M et al. 2019. Basophil-derived tumor necrosis factor can enhance survival in a sepsis model in mice. Nat. Immunol. 20:129–40
    [Google Scholar]
  58. 58. 
    Geering B, Stoeckle C, Conus S, Simon HU 2013. Living and dying for inflammation: neutrophils, eosinophils, basophils. Trends Immunol 34:398–409
    [Google Scholar]
  59. 59. 
    Sonoda T, Kanayama Y, Hara H, Hayashi C, Tadokoro M et al. 1984. Proliferation of peritoneal mast cells in the skin of W/Wv mice that genetically lack mast cells. J. Exp. Med. 160:138–51
    [Google Scholar]
  60. 60. 
    Tsai M, Shih LS, Newlands GF, Takeishi T, Langley KE et al. 1991. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo: analysis by anatomical distribution, histochemistry, and protease phenotype. J. Exp. Med. 174:125–31
    [Google Scholar]
  61. 61. 
    Tsai M, Takeishi T, Thompson H, Langley KE, Zsebo KM et al. 1991. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. PNAS 88:6382–86
    [Google Scholar]
  62. 62. 
    Kambe N, Kambe M, Kochan JP, Schwartz LB 2001. Human skin–derived mast cells can proliferate while retaining their characteristic functional and protease phenotypes. Blood 97:2045–52
    [Google Scholar]
  63. 63. 
    Suurmond J, Habets KLL, Tatum Z, Schonkeren JJ, Hoen PAC et al. 2016. Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue. J. Allergy Clin. Immunol. 138:869–80
    [Google Scholar]
  64. 64. 
    Arinobu Y, Iwasaki H, Gurish MF, Mizuno S, Shigematsu H et al. 2005. Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. PNAS 102:18105–10
    [Google Scholar]
  65. 65. 
    Chen CC, Grimbaldeston MA, Tsai M, Weissman IL, Galli SJ 2005. Identification of mast cell progenitors in adult mice. PNAS 102:11408–13
    [Google Scholar]
  66. 66. 
    Franco CB, Chen CC, Drukker M, Weissman IL, Galli SJ 2010. Distinguishing mast cell and granulocyte differentiation at the single-cell level. Cell Stem Cell 6:361–68
    [Google Scholar]
  67. 67. 
    Mukai K, BenBarak MJ, Tachibana M, Nishida K, Karasuyama H et al. 2012. Critical role of P1-Runx1 in mouse basophil development. Blood 120:76–85
    [Google Scholar]
  68. 68. 
    Metcalf D, Ng AP, Baldwin TM, Di Rago L, Mifsud S 2013. Concordant mast cell and basophil production by individual hematopoietic blast colony-forming cells. PNAS 110:9031–35
    [Google Scholar]
  69. 69. 
    Qi X, Hong J, Chaves L, Zhuang Y, Chen Y et al. 2013. Antagonistic regulation by the transcription factors C/EBPα and MITF specifies basophil and mast cell fates. Immunity 39:97–110
    [Google Scholar]
  70. 70. 
    Sasaki H, Kurotaki D, Osato N, Sato H, Sasaki I et al. 2015. Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells. Blood 125:358–69
    [Google Scholar]
  71. 71. 
    Huang H, Li Y, Liu B 2016. Transcriptional regulation of mast cell and basophil lineage commitment. Semin. Immunopathol. 38:539–48
    [Google Scholar]
  72. 72. 
    Kashem SW, Subramanian H, Collington SJ, Magotti P, Lambris JD, Ali H 2011. G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2. Eur. J. Pharmacol. 668:299–304
    [Google Scholar]
  73. 73. 
    Johnson-Weaver B, Choi HW, Abraham SN, Staats HF 2018. Mast cell activators as novel immune regulators. Curr. Opin. Pharmacol. 41:89–95
    [Google Scholar]
  74. 74. 
    Selye H. 1965. The Mast Cells Washington, DC: Butterworth498 pp.
    [Google Scholar]
  75. 75. 
    Nakano T, Sonoda T, Hayashi C, Yamatodani A, Kanayama Y et al. 1985. Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice: evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J. Exp. Med. 162:1025–43
    [Google Scholar]
  76. 76. 
    Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ 2005. Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am. J. Pathol. 167:835–48
    [Google Scholar]
  77. 77. 
    Wershil BK, Furuta GT, Wang ZS, Galli SJ 1996. Mast cell-dependent neutrophil and mononuclear cell recruitment in immunoglobulin E-induced gastric reactions in mice. Gastroenterology 110:1482–90
    [Google Scholar]
  78. 78. 
    Brown MA, Tanzola MB, Robbie-Ryan M 2002. Mechanisms underlying mast cell influence on EAE disease course. Mol. Immunol. 38:1373–78
    [Google Scholar]
  79. 79. 
    Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G 2015. Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv. Immunol. 126:45–127
    [Google Scholar]
  80. 80. 
    Reber LL, Marichal T, Galli SJ 2012. New models for analyzing mast cell functions in vivo. Trends Immunol 33:613–25
    [Google Scholar]
  81. 81. 
    Hammel I, Lagunoff D, Galli SJ 2010. Regulation of secretory granule size by the precise generation and fusion of unit granules. J. Cell Mol. Med. 14:1904–16
    [Google Scholar]
  82. 82. 
    Jippo T, Lee YM, Ge Y, Kim DK, Okabe M, Kitamura Y 2001. Tissue-dependent alteration of protease expression phenotype in murine peritoneal mast cells that were genetically labeled with green fluorescent protein. Am. J. Pathol. 158:1695–701
    [Google Scholar]
  83. 83. 
    Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ 2006. Mast cells can promote the development of multiple features of chronic asthma in mice. J. Clin. Investig. 116:1633–41
    [Google Scholar]
  84. 84. 
    Yu M, Eckart MR, Morgan AA, Mukai K, Butte AJ et al. 2011. Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma. J. Clin. Investig. 121:3133–43
    [Google Scholar]
  85. 85. 
    Wershil BK, Tsai M, Geissler EN, Zsebo KM, Galli SJ 1992. The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo: evidence that signaling through the c-kit receptor can induce expression of cellular function. J. Exp. Med. 175:245–55
    [Google Scholar]
  86. 86. 
    Blankenhaus B, Reitz M, Brenz Y, Eschbach ML, Hartmann W et al. 2014. Foxp3+ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice. PLOS Pathog 10:e1003913
    [Google Scholar]
  87. 87. 
    Gomez-Pinilla PJ, Farro G, Di Giovangiulio M, Stakenborg N, Nemethova A et al. 2014. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation. PLOS ONE 9:e85304
    [Google Scholar]
  88. 88. 
    Mukai K, Karasuyama H, Kabashima K, Kubo M, Galli SJ 2017. Differences in the importance of mast cells, basophils, IgE, and IgG versus that of CD4+ T cells and ILC2 cells in primary and secondary immunity to Strongyloides venezuelensis. Infect. Immun 85:e00053–17
    [Google Scholar]
  89. 89. 
    Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N et al. 2011. Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 35:832–44
    [Google Scholar]
  90. 90. 
    Arac A, Grimbaldeston MA, Nepomuceno AR, Olayiwola O, Pereira MP et al. 2014. Evidence that meningeal mast cells can worsen stroke pathology in mice. Am. J. Pathol. 184:2493–504
    [Google Scholar]
  91. 91. 
    Lilla JN, Chen CC, Mukai K, BenBarak MJ, Franco CB et al. 2011. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice. Blood 118:6930–38
    [Google Scholar]
  92. 92. 
    Dudeck A, Dudeck J, Scholten J, Petzold A, Surianarayanan S et al. 2011. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity 34:973–84
    [Google Scholar]
  93. 93. 
    Otsuka A, Kubo M, Honda T, Egawa G, Nakajima S et al. 2011. Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity. PLOS ONE 6:e25538
    [Google Scholar]
  94. 94. 
    Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K et al. 2012. Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness. J. Immunol. 188:1809–18
    [Google Scholar]
  95. 95. 
    Reber LL, Marichal T, Mukai K, Kita Y, Tokuoka SM et al. 2013. Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice. J. Allergy Clin. Immunol. 132:881–88.e11
    [Google Scholar]
  96. 96. 
    Heger K, Seidler B, Vahl JC, Schwartz C, Kober M et al. 2014. CreERT2 expression from within the c-Kit gene locus allows efficient inducible gene targeting in and ablation of mast cells. Eur. J. Immunol. 44:296–306
    [Google Scholar]
  97. 97. 
    Forster A, Blissenbach B, Machova A, Leja S, Rabenhorst A et al. 2015. Dicer is indispensable for the development of murine mast cells. J. Allergy Clin. Immunol. 135:1077–80.e4
    [Google Scholar]
  98. 98. 
    Reitz M, Brunn ML, Rodewald HR, Feyerabend TB, Roers A et al. 2017. Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection. Mucosal Immunol 10:481–92
    [Google Scholar]
  99. 99. 
    Becker M, Reuter S, Friedrich P, Doener F, Michel A et al. 2011. Genetic variation determines mast cell functions in experimental asthma. J. Immunol. 186:7225–31
    [Google Scholar]
  100. 99a. 
    Hernandez JD, Yu M, Sibilano R, Tsai M, Galli SJ 2019. Development of multiple features of antigen-induced asthma pathology in a new strain of mast cell deficient BALB/c-KitW-sh/W-sh mice. Lab. Investig In press
    [Google Scholar]
  101. 100. 
    Cheng LE, Hartmann K, Roers A, Krummel MF, Locksley RM 2013. Perivascular mast cells dynamically probe cutaneous blood vessels to capture immunoglobulin E. Immunity 38:166–75
    [Google Scholar]
  102. 101. 
    Reber LL, Sibilano R, Starkl P, Roers A, Grimbaldeston MA et al. 2017. Imaging protective mast cells in living mice during severe contact hypersensitivity. JCI Insight 2:e92900
    [Google Scholar]
  103. 102. 
    Dudeck J, Medyukhina A, Frobel J, Svensson CM, Kotrba J et al. 2017. Mast cells acquire MHCII from dendritic cells during skin inflammation. J. Exp. Med. 214:3791–811
    [Google Scholar]
  104. 103. 
    Gaudenzio N, Marichal T, Galli SJ, Reber LL 2018. Genetic and imaging approaches reveal pro-inflammatory and immunoregulatory roles of mast cells in contact hypersensitivity. Front. Immunol. 9:1275
    [Google Scholar]
  105. 104. 
    Ayyadurai S, Gibson AJ, D'Costa S, Overman EL, Sommerville LJ et al. 2017. Frontline science: Corticotropin-releasing factor receptor subtype 1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology. J. Leukoc. Biol. 102:1299–312
    [Google Scholar]
  106. 105. 
    Bulfone-Paus S, Nilsson G, Draber P, Blank U, Levi-Schaffer F 2017. Positive and negative signals in mast cell activation. Trends Immunol 38:657–67
    [Google Scholar]
  107. 106. 
    D'Costa S, Ayyadurai S, Gibson AJ, Mackey E, Rajput M et al. 2019. Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability. J. Allergy Clin. Immunol. 143:1865–77.e4
    [Google Scholar]
  108. 107. 
    Subramanian H, Gupta K, Guo Q, Price R, Ali H 2011. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization. J. Biol. Chem. 286:44739–49
    [Google Scholar]
  109. 108. 
    Meixiong J, Dong X. 2017. Mas-related G protein-coupled receptors and the biology of itch sensation. Annu. Rev. Genet. 51:103–21
    [Google Scholar]
  110. 109. 
    Ali H. 2017. Emerging roles for MAS-related G protein-coupled receptor-X2 in host defense peptide, opioid, and neuropeptide-mediated inflammatory reactions. Adv. Immunol. 136:123–62
    [Google Scholar]
  111. 110. 
    McNeil BD, Pundir P, Meeker S, Han L, Undem BJ et al. 2015. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature 519:237–41
    [Google Scholar]
  112. 111. 
    Subramanian H, Gupta K, Ali H 2016. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J. Allergy Clin. Immunol. 138:700–10
    [Google Scholar]
  113. 112. 
    Solley GO, Gleich GJ, Jordon RE, Schroeter AL 1976. The late phase of the immediate wheal and flare skin reaction: its dependence upon IgE antibodies. J. Clin. Investig. 58:408–20
    [Google Scholar]
  114. 113. 
    Cohan VL, MacGlashan DW Jr, Warner JA, Lichtenstein LM, Proud D 1991. Mechanisms of mediator release from human skin mast cells upon stimulation by the bradykinin analog, [dArg0-Hyp3-dPhe7]bradykinin. Biochem. Pharmacol 41:293–300
    [Google Scholar]
  115. 114. 
    Arifuzzaman M, Mobley YR, Choi HW, Bist P, Salinas CA et al. 2019. MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection. Sci. Adv. 5:eaav0216
    [Google Scholar]
  116. 115. 
    Pundir P, Liu R, Vasavda C, Serhan N, Limjunyawong N et al. 2019. A connective tissue mast-cell-specific receptor detects bacterial quorum-sensing molecules and mediates antibacterial immunity. Cell Host Microbe 26:114–22
    [Google Scholar]
  117. 116. 
    Arizono N, Matsuda S, Hattori T, Kojima Y, Maeda T, Galli SJ 1990. Anatomical variation in mast cell nerve associations in the rat small intestine, heart, lung, and skin. Similarities of distances between neural processes and mast cells, eosinophils, or plasma cells in the jejunal lamina propria. Lab Investig 62:626–34
    [Google Scholar]
  118. 117. 
    Alving K, Sundstrom C, Matran R, Panula P, Hokfelt T, Lundberg JM 1991. Association between histamine-containing mast cells and sensory nerves in the skin and airways of control and capsaicin-treated pigs. Cell Tissue Res 264:529–38
    [Google Scholar]
  119. 118. 
    Pang X, Boucher W, Triadafilopoulos G, Sant GR, Theoharides TC 1996. Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Urology 47:436–38
    [Google Scholar]
  120. 119. 
    Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS et al. 2004. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 126:693–702
    [Google Scholar]
  121. 120. 
    Kakurai M, Monteforte R, Suto H, Tsai M, Nakae S, Galli SJ 2006. Mast cell-derived tumor necrosis factor can promote nerve fiber elongation in the skin during contact hypersensitivity in mice. Am. J. Pathol. 169:1713–21
    [Google Scholar]
  122. 121. 
    Hagiyama M, Inoue T, Furuno T, Iino T, Itami S et al. 2013. Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis. Br. J. Dermatol. 168:771–78
    [Google Scholar]
  123. 122. 
    Suzuki R, Furuno T, McKay DM, Wolvers D, Teshima R et al. 1999. Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. J. Immunol. 163:2410–15
    [Google Scholar]
  124. 123. 
    Perdue MH, Masson S, Wershil BK, Galli SJ 1991. Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis: correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation. J. Clin. Investig. 87:687–93
    [Google Scholar]
  125. 124. 
    Buhner S, Barki N, Greiter W, Giesbertz P, Demir IE et al. 2017. Calcium imaging of nerve-mast cell signaling in the human intestine. Front. Physiol. 8:971
    [Google Scholar]
  126. 125. 
    Green DP, Limjunyawong N, Gour N, Pundir P, Dong X 2019. A mast-cell-specific receptor mediates neurogenic inflammation and pain. Neuron 101:412–20.e3
    [Google Scholar]
  127. 126. 
    Meixiong J, Anderson M, Limjunyawong N, Sabbagh MF, Hu E et al. 2019. Activation of mast-cell-expressed mas-related G-protein-coupled receptors drives non-histaminergic itch. Immunity 50:1163–71.e5
    [Google Scholar]
  128. 127. 
    Hajishengallis G, Reis ES, Mastellos DC, Ricklin D, Lambris JD 2017. Novel mechanisms and functions of complement. Nat. Immunol. 18:1288–98
    [Google Scholar]
  129. 128. 
    Wershil BK, Mekori YA, Murakami T, Galli SJ 1987. 125I-fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin: demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells. J. Immunol. 139:2605–14
    [Google Scholar]
  130. 129. 
    Kobayashi T, Miura T, Haba T, Sato M, Serizawa I et al. 2000. An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model. J. Immunol. 164:3855–61
    [Google Scholar]
  131. 130. 
    Williams CMM, Galli SJ. 2000. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J. Exp. Med. 192:455–62
    [Google Scholar]
  132. 131. 
    Nakae S, Ho LH, Yu M, Monteforte R, Iikura M et al. 2007. Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice. J. Allergy Clin. Immunol. 120:48–55
    [Google Scholar]
  133. 132. 
    Sibilano R, Gaudenzio N, DeGorter MK, Reber LL, Hernandez JD et al. 2016. A TNFRSF14-FcvarεRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice. Nat. Commun. 7:13696
    [Google Scholar]
  134. 133. 
    Yu M, Mukai K, Tsai M, Galli SJ 2018. Thirdhand smoke component can exacerbate a mouse asthma model through mast cells. J. Allergy Clin. Immunol. 142:1618–27.e9
    [Google Scholar]
  135. 134. 
    Arias K, Chu DK, Flader K, Botelho F, Walker T et al. 2011. Distinct immune effector pathways contribute to the full expression of peanut-induced anaphylactic reactions in mice. J. Allergy Clin. Immunol. 127:1552–61.e1
    [Google Scholar]
  136. 135. 
    Wang Q, Lepus CM, Raghu H, Reber LL, Tsai MM et al. 2019. IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis. eLife 8:e39905
    [Google Scholar]
  137. 136. 
    Benede S, Berin MC. 2018. Mast cell heterogeneity underlies different manifestations of food allergy in mice. PLOS ONE 13:e0190453
    [Google Scholar]
  138. 137. 
    Mukai K, Matsuoka K, Taya C, Suzuki H, Yokozeki H et al. 2005. Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity 23:191–202
    [Google Scholar]
  139. 138. 
    Ohnmacht C, Schwartz C, Panzer M, Schiedewitz I, Naumann R, Voehringer D 2010. Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Immunity 33:364–74
    [Google Scholar]
  140. 139. 
    Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T et al. 2010. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. J. Clin. Investig. 120:2867–75
    [Google Scholar]
  141. 140. 
    Sullivan BM, Liang HE, Bando JK, Wu D, Cheng LE et al. 2011. Genetic analysis of basophil function in vivo. Nat. Immunol. 12:527–35
    [Google Scholar]
  142. 141. 
    Serhan N, Basso L, Sibilano R, Petitfils C, Meixiong J et al. 2019. House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation. Nat. Immunol. 20:1435–43 https://doi.org/10.1038/s41590-019-0493-z
    [Crossref] [Google Scholar]
  143. 142. 
    Sun J, Sukhova GK, Wolters PJ, Yang M, Kitamoto S et al. 2007. Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat. Med. 13:719–24
    [Google Scholar]
  144. 143. 
    Liu J, Divoux A, Sun J, Zhang J, Clement K et al. 2009. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15:940–45
    [Google Scholar]
  145. 144. 
    Gutierrez DA, Fu W, Schonefeldt S, Feyerabend TB, Ortiz-Lopez A et al. 2014. Type 1 diabetes in NOD mice unaffected by mast cell deficiency. Diabetes 63:3827–34
    [Google Scholar]
  146. 145. 
    Gutierrez DA, Muralidhar S, Feyerabend TB, Herzig S, Rodewald HR 2015. Hematopoietic kit deficiency, rather than lack of mast cells, protects mice from obesity and insulin resistance. Cell Metab 21:678–91
    [Google Scholar]
  147. 146. 
    Khan AI, Horii Y, Tiuria R, Sato Y, Nawa Y 1993. Mucosal mast cells and the expulsive mechanisms of mice against Strongyloides venezuelensis. Int. J. Parasitol 23:551–55
    [Google Scholar]
  148. 147. 
    Lantz CS, Boesiger J, Song CH, Mach N, Kobayashi T et al. 1998. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392:90–93
    [Google Scholar]
  149. 148. 
    Sasaki Y, Yoshimoto T, Maruyama H, Tegoshi T, Ohta N et al. 2005. IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. J. Exp. Med. 202:607–16
    [Google Scholar]
  150. 149. 
    Abe T, Nawa Y. 1987. Reconstitution of mucosal mast cells in W/Wv mice by adoptive transfer of bone marrow-derived cultured mast cells and its effects on the protective capacity to Strongyloides ratti-infection. Parasite Immunol 9:31–38
    [Google Scholar]
  151. 150. 
    Abe T, Nawa Y. 1987. Localization of mucosal mast cells in W/Wv mice after reconstitution with bone marrow cells or cultured mast cells, and its relation to the protective capacity to Strongyloides ratti infection. Parasite Immunol 9:477–85
    [Google Scholar]
  152. 151. 
    Schneider LA, Schlenner SM, Feyerabend TB, Wunderlin M, Rodewald HR 2007. Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin. J. Exp. Med. 204:2629–39
    [Google Scholar]
  153. 152. 
    Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ 2007. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat. Immunol. 8:1095–104
    [Google Scholar]
  154. 153. 
    Galli SJ, Hammel I. 1984. Unequivocal delayed hypersensitivity in mast cell-deficient and beige mice. Science 226:710–13
    [Google Scholar]
  155. 154. 
    Bryce PJ, Miller ML, Miyajima I, Tsai M, Galli SJ, Oettgen HC 2004. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity 20:381–92
    [Google Scholar]
  156. 155. 
    Norman MU, Hwang J, Hulliger S, Bonder CS, Yamanouchi J et al. 2008. Mast cells regulate the magnitude and the cytokine microenvironment of the contact hypersensitivity response. Am. J. Pathol. 172:1638–49
    [Google Scholar]
  157. 156. 
    Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA et al. 2000. Mast cells control neutrophil recruitment during T cell–mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. J. Exp. Med. 192:1441–52
    [Google Scholar]
  158. 157. 
    Chan CY St, John AL, Abraham SN. 2013. Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38:349–59
    [Google Scholar]
  159. 158. 
    Dutta NK, Narayanan KG. 1952. Release of histamine from rat diaphragm by cobra venom. Nature 169:1064–65
    [Google Scholar]
  160. 159. 
    Weisel-Eichler A, Libersat F. 2004. Venom effects on monoaminergic systems. J. Comp. Physiol. A 190:683–90
    [Google Scholar]
  161. 160. 
    Galli SJ, Tsai M, Piliponsky AM 2008. The development of allergic inflammation. Nature 454:445–54
    [Google Scholar]
  162. 161. 
    Galli SJ, Tsai M. 2012. IgE and mast cells in allergic disease. Nat. Med. 18:693–704
    [Google Scholar]
  163. 162. 
    Bradding P, Arthur G. 2016. Mast cells in asthma–state of the art. Clin. Exp. Allergy 46:194–263
    [Google Scholar]
  164. 163. 
    Renz H, Allen KJ, Sicherer SH, Sampson HA, Lack G et al. 2018. Food allergy. Nat. Rev. Dis. Primers 4:17098
    [Google Scholar]
  165. 164. 
    Djukanovic R, Wilson SJ, Kraft M, Jarjour NN, Steel M et al. 2004. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am. J. Respir. Crit. Care Med. 170:583–93
    [Google Scholar]
  166. 165. 
    Galli SJ. 2017. Mast cells and KIT as potential therapeutic targets in severe asthma. N. Engl. J. Med. 376:1983–84
    [Google Scholar]
  167. 166. 
    Cahill KN, Katz HR, Cui J, Lai J, Kazani S et al. 2017. KIT inhibition by imatinib in patients with severe refractory asthma. N. Engl. J. Med. 376:1911–20
    [Google Scholar]
  168. 167. 
    Holgate ST. 2011. Pathophysiology of asthma: What has our current understanding taught us about new therapeutic approaches. ? J. Allergy Clin. Immunol. 128:495–505
    [Google Scholar]
  169. 168. 
    Zhou JS, Xing W, Friend DS, Austen KF, Katz HR 2007. Mast cell deficiency in KitW-sh mice does not impair antibody-mediated arthritis. J. Exp. Med. 204:2797–802
    [Google Scholar]
  170. 169. 
    Nauta AC, Grova M, Montoro DT, Zimmermann A, Tsai M et al. 2013. Evidence that mast cells are not required for healing of splinted cutaneous excisional wounds in mice. PLOS ONE 8:e59167
    [Google Scholar]
  171. 170. 
    Antsiferova M, Martin C, Huber M, Feyerabend TB, Forster A et al. 2013. Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis. J. Immunol. 191:6147–55
    [Google Scholar]
  172. 171. 
    Willenborg S, Eckes B, Brinckmann J, Krieg T, Waisman A et al. 2014. Genetic ablation of mast cells redefines the role of mast cells in skin wound healing and bleomycin-induced fibrosis. J. Investig. Dermatol. 134:2005–15
    [Google Scholar]
  173. 172. 
    Chmelar J, Chatzigeorgiou A, Chung KJ, Prucnal M, Voehringer D et al. 2016. No role for mast cells in obesity-related metabolic dysregulation. Front. Immunol. 7:524
    [Google Scholar]
  174. 173. 
    Brown MA. 2018. Studies of mast cells: adventures in serendipity. Front. Immunol. 9:520
    [Google Scholar]
  175. 174. 
    Battey J, Jordan E, Cox D, Dove W 1999. An action plan for mouse genomics. Nat. Genet. 21:73–75
    [Google Scholar]
  176. 175. 
    Mouse Genome Seq. Consort. Waterston RH, Lindblad-Toh K, Birney E, Rogers J et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–62
    [Google Scholar]
  177. 176. 
    Cerny-Reiterer S, Rabenhorst A, Stefanzl G, Herndlhofer S, Hoermann G et al. 2015. Long-term treatment with imatinib results in profound mast cell deficiency in Ph+ chronic myeloid leukemia. Oncotarget 6:3071–84
    [Google Scholar]
  178. 177. 
    Choi HW, Suwanpradid J, Kim IH, Staats HF, Haniffa M et al. 2018. Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles. Science 362:eaao0666
    [Google Scholar]
  179. 178. 
    Kim DK, Cho YE, Komarow HD, Bandara G, Song BJ et al. 2018. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their activation. PNAS 115:E10692–701
    [Google Scholar]
  180. 179. 
    Kitamura Y, Go S, Hatanaka K 1978. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52:447–52
    [Google Scholar]
  181. 180. 
    Waskow C, Bartels S, Schlenner SM, Costa C, Rodewald HR 2007. Kit is essential for PMA-inflammation-induced mast-cell accumulation in the skin. Blood 109:5363–70
    [Google Scholar]
  182. 181. 
    Mancardi DA, Jonsson F, Iannascoli B, Khun H, Van Rooijen N et al. 2011. Cutting edge: The murine high-affinity IgG receptor FcγRIV is sufficient for autoantibody-induced arthritis. J. Immunol. 186:1899–903
    [Google Scholar]
  183. 182. 
    Nigrovic PA, Gray DH, Jones T, Hallgren J, Kuo FC et al. 2008. Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am. J. Pathol. 173:1693–701
    [Google Scholar]
  184. 183. 
    Piliponsky AM, Chen CC, Grimbaldeston MA, Burns-Guydish SM, Hardy J et al. 2010. Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am. J. Pathol. 176:926–38
    [Google Scholar]
  185. 184. 
    Michel A, Schuler A, Friedrich P, Doner F, Bopp T et al. 2013. Mast cell-deficient KitW-sh “Sash” mutant mice display aberrant myelopoiesis leading to the accumulation of splenocytes that act as myeloid-derived suppressor cells. J. Immunol. 190:5534–44
    [Google Scholar]
  186. 185. 
    Reber LL, Marichal T, Sokolove J, Starkl P, Gaudenzio N et al. 2014. Contribution of mast cell-derived interleukin-1β to uric acid crystal-induced acute arthritis in mice. Arthritis Rheumatol 66:2881–91
    [Google Scholar]
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