[en] Contact hypersensitivity (CHS) is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo. Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Gaudenzio, Nicolas
Marichal, Thomas ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Galli, Stephen J.
Reber, Laurent L.
Language :
English
Title :
Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity.
Publication date :
2018
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Research Foundation, Lausanne, Switzerland
Belsito DV. A sherlockian approach to contact dermatitis. Dermatol Clin (1999) 17:705-13, x. doi:10.1016/S0733-8635(05)70117-0
Grabbe S, Schwarz T. Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today (1998) 19:37-44. doi:10.1016/S0167-5699(97)01186-9
Vocanson M, Hennino A, Rozieres A, Poyet G, Nicolas JF. Effector and regulatory mechanisms in allergic contact dermatitis. Allergy (2009) 64:1699-714. doi:10.1111/j.1398-9995.2009.02082.x
Weber FC, Nemeth T, Csepregi JZ, Dudeck A, Roers A, Ozsvari B, et al. Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity. J Exp Med (2015) 212:15-22. doi:10.1084/jem.20130062
O'Leary JG, Goodarzi M, Drayton DL, von Andrian UH. T cell-and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol (2006) 7:507-16. doi:10.1038/ni1332
Rafei-Shamsabadi DA, van de Poel S, Dorn B, Kunz S, Martin SF, Klose CSN, et al. Lack of type 2 innate lymphoid cells promote a type I driven enhanced immune response in contact hypersensitivity. J Invest Dermatol (2018). doi:10.1016/j.jid.2018.03.001
Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol (2010) 10:440-52. doi:10.1038/nri2782
Reber LL, Frossard N. Targeting mast cells in inflammatory diseases. Pharmacol Ther (2014) 142:416-35. doi:10.1016/j.pharmthera.2014.01.004
Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol (2008) 8:478-86. doi:10.1038/nri2327
Galli SJ, Nakae S, Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol (2005) 6:135-42. doi:10.1038/ni1158
Galli SJ, KalesnikoffJ, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M. Mast cells as "tunable" effector and immunoregulatory cells: recent advances. Annu Rev Immunol (2005) 23:749-86. doi:10.1146/annurev.immunol.21.120601.141025
Rodewald HR, Feyerabend TB. Widespread immunological functions of mast cells: fact or fiction? Immunity (2012) 37:13-24. doi:10.1016/j.immuni.2012.07.007
Reber LL, Marichal T, Galli SJ. New models for analyzing mast cell functions in vivo. Trends Immunol (2012) 33:613-25. doi:10.1016/j.it.2012.09.008
Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood (1978) 52:447-52
Oliveira SH, Lukacs NW. Stem cell factor: a hemopoietic cytokine with important targets in asthma. Curr Drug Targets Inflamm Allergy (2003) 2:313-8. doi:10.2174/1568010033483990
Reber L, Da Silva CA, Frossard N. Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharmacol (2006) 533:327-40. doi:10.1016/j.ejphar.2005.12.067
Dawicki W, Marshall JS. New and emerging roles for mast cells in host defence. Curr Opin Immunol (2007) 19:31-8. doi:10.1016/j.coi.2006.11.006
Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol (2005) 167:835-48. doi:10.1016/S0002-9440(10)62055-X
Kitamura Y. Heterogeneity of mast cells and phenotypic change between subpopulations. Annu Rev Immunol (1989) 7:59-76. doi:10.1146/annurev.iy.07.040189.000423
Piliponsky AM, Chen CC, Grimbaldeston MA, Burns-Guydish SM, Hardy J, KalesnikoffJ, et al. Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am J Pathol (2010) 176:926-38. doi:10.2353/ajpath.2010.090342
Grimbaldeston MA, Metz M, Yu M, Tsai M, Galli SJ. Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses. Curr Opin Immunol (2006) 18:751-60. doi:10.1016/j.coi.2006.09.011
Nakano T, Sonoda T, Hayashi C, Yamatodani A, Kanayama Y, Yamamura T, et al. 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 (1985) 162:1025-43
Galli SJ, Tsai M, Marichal T, Tchougounova E, Reber LL, Pejler G. Approaches for analyzing the roles of mast cells and their proteases in vivo. Adv Immunol (2015) 126:45-127. doi:10.1016/bs.ai.2014.11.002
Dudeck A, Dudeck J, Scholten J, Petzold A, Surianarayanan S, Kohler A, et al. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity (2011) 34:973-84. doi:10.1016/j.immuni.2011.03.028
Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N, Kopf M, et al. Cre-mediated cell ablation contests mast cell contribution in models of antibody-and T cell-mediated autoimmunity. Immunity (2011) 35:832-44. doi:10.1016/j.immuni.2011.09.015
Lilla JN, Chen CC, Mukai K, BenBarak MJ, Franco CB, KalesnikoffJ, et al. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/flmice. Blood (2011) 118:6930-8. doi:10.1182/blood-2011-03-343962
Otsuka A, Kubo M, Honda T, Egawa G, Nakajima S, Tanizaki H, et al. Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity. PLoS One (2011) 6:e25538. doi:10.1371/journal.pone.0025538
Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, et al. Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness. J Immunol (2012) 188:1809-18. doi:10.4049/jimmunol.1101746
Dahdah A, Gautier G, Attout T, Fiore F, Lebourdais E, Msallam R, et al. Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis. J Clin Invest (2014) 124:4577-89. doi:10.1172/JCI75212
Feyerabend TB, Terszowski G, Tietz A, Blum C, Luche H, Gossler A, et al. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity (2009) 30:67-79. doi:10.1016/j.immuni.2008.10.016
Furumoto Y, Charles N, Olivera A, Leung WH, Dillahunt S, Sargent JL, et al. PTEN deficiency in mast cells causes a mastocytosis-like proliferative disease that heightens allergic responses and vascular permeability. Blood (2011) 118:5466-75. doi:10.1182/blood-2010-09-309955
Musch W, Wege AK, Mannel DN, Hehlgans T. Generation and characterization of alpha-chymase-Cre transgenic mice. Genesis (2008) 46:163-6. doi:10.1002/dvg.20378
Scholten J, Hartmann K, Gerbaulet A, Krieg T, Muller W, Testa G, et al. Mast cell-specific Cre/loxP-mediated recombination in vivo. Transgenic Res (2008) 17:307-15. doi:10.1007/s11248-007-9153-4
Li Y, Liu B, Harmacek L, Long Z, Liang J, Lukin K, et al. The transcription factors GATA2 and MITF regulate Hdc gene expression in mast cells and are required for IgE/mast cell-mediated anaphylaxis. J Allergy Clin Immunol (2017). doi:10.1016/j.jaci.2017.10.043
Pejler G, Ronnberg E, Waern I, Wernersson S. Mast cell proteases: multifaceted regulators of inflammatory disease. Blood (2010) 115:4981-90. doi:10.1182/blood-2010-01-257287
Shimshek DR, Kim J, Hubner MR, Spergel DJ, Buchholz F, Casanova E, et al. Codon-improved Cre recombinase (iCre) expression in the mouse. Genesis (2002) 32:19-26. doi:10.1002/gene.10023
Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol (2001) 1:4. doi:10.1186/1471-213X-1-4
Gaudenzio N, Sibilano R, Marichal T, Starkl P, Reber LL, Cenac N, et al. Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest (2016) 126:3981-98. doi:10.1172/JCI85538
Reber LL, Sibilano R, Starkl P, Roers A, Grimbaldeston MA, Tsai M, et al. Imaging protective mast cells in living mice during severe contact hypersensitivity. JCI Insight (2017) 2:e92900. doi:10.1172/jci.insight.92900
Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci (2010) 13:133-40. doi:10.1038/nn.2467
Cheng LE, Hartmann K, Roers A, Krummel MF, Locksley RM. Perivascular mast cells dynamically probe cutaneous blood vessels to capture immunoglobulin E. Immunity (2013) 38:166-75. doi:10.1016/j.immuni.2012.09.022
Luche H, Weber O, Nageswara Rao T, Blum C, Fehling HJ. Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage tracing studies. Eur J Immunol (2007) 37:43-53. doi:10.1002/eji.200636745
Dudeck J, Medyukhina A, Frobel J, Svensson CM, Kotrba J, Gerlach M, et al. Mast cells acquire MHCII from dendritic cells during skin inflammation. J Exp Med (2017) 214:3791-811. doi:10.1084/jem.20160783
Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, Sparwasser T, et al. In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity (2002) 17:211-20. doi:10.1016/S1074-7613(02)00365-5
Shaner NC, Campbell RE, Steinbach PA, Giepmans BN, Palmer AE, Tsien RY. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol (2004) 22:1567-72. doi:10.1038/nbt1037
Drew E, Merzaban JS, Seo W, Ziltener HJ, McNagny KM. CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution. Immunity (2005) 22:43-57. doi:10.1016/j.immuni.2004.11.014
Kinet JP, Blank U, Ra C, White K, Metzger H, Kochan J. Isolation and characterization of cDNAs coding for the beta subunit of the high-affinity receptor for immunoglobulin E. Proc Natl Acad Sci U S A (1988) 85:6483-7. doi:10.1073/pnas.85.17.6483
Bulfone-Paus S, Nilsson G, Draber P, Blank U, Levi-Schaffer F. Positive and negative signals in mast cell activation. Trends Immunol (2017) 38(9):657-67. doi:10.1016/j.it.2017.01.008
Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol (2011) 12:1035-44. doi:10.1038/ni.2109
Joulia R, Gaudenzio N, Rodrigues M, Lopez J, Blanchard N, Valitutti S, et al. Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence. Nat Commun (2015) 6:6174. doi:10.1038/ncomms7174
Sali A, Matsumoto R, McNeil HP, Karplus M, Stevens RL. Three-dimensional models of four mouse mast cell chymases. Identification of proteoglycan binding regions and protease-specific antigenic epitopes. J Biol Chem (1993) 268:9023-34
Stevens RL, Fox CC, Lichtenstein LM, Austen KF. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells. Proc Natl Acad Sci U S A (1988) 85:2284-7. doi:10.1073/pnas.85.7.2284
Tharp MD, Seelig LL, Tigelaar RE, Bergstresser PR. Conjugated avidin binds to mast-cell granules. J Histochem Cytochem (1985) 33:27-32. doi:10.1177/33.1.2578142
Joulia R, L'Faqihi FE, Valitutti S, Espinosa E. IL-33 fine tunes mast cell degranulation and chemokine production at the single-cell level. J Allergy Clin Immunol (2017) 140(2):497-509.e10. doi:10.1016/j.jaci.2016.09.049
McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature (2014) 519:237-41. doi:10.1038/nature14022
Askenase PW, Van Loveren H, Kraeuter-Kops S, Ron Y, Meade R, Theoharides TC, et al. Defective elicitation of delayed-type hypersensitivity in W/Wv and SI/SId mast cell-deficient mice. J Immunol (1983) 131:2687-94
Biedermann T, Kneilling M, Mailhammer R, Maier K, Sander CA, Kollias G, et al. 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 (2000) 192:1441-52. doi:10.1084/jem.192.10.1441
Bryce PJ, Miller ML, Miyajima I, Tsai M, Galli SJ, Oettgen HC. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity (2004) 20:381-92. doi:10.1016/S1074-7613(04)00080-9
Dudeck J, Ghouse SM, Lehmann CH, Hoppe A, Schubert N, Nedospasov SA, et al. Mast-cell-derived TNF amplifies CD8(+) dendritic cell functionality and CD8(+) T cell priming. Cell Rep (2015) 13:399-411. doi:10.1016/j.celrep.2015.08.078
Norman MU, Hwang J, Hulliger S, Bonder CS, Yamanouchi J, Santamaria P, et al. Mast cells regulate the magnitude and the cytokine microenvironment of the contact hypersensitivity response. Am J Pathol (2008) 172:1638-49. doi:10.2353/ajpath.2008.070559
Grimbaldeston MA, Nakae S, KalesnikoffJ, Tsai M, Galli SJ. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol (2007) 8:1095-104. doi:10.1038/ni1503
Hershko AY, Suzuki R, Charles N, Alvarez-Errico D, Sargent JL, Laurence A, et al. Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity (2011) 35:562-71. doi:10.1016/j.immuni.2011.07.013
Gimenez-Rivera VA, Siebenhaar F, Zimmermann C, Siiskonen H, Metz M, Maurer M. Mast cells limit the exacerbation of chronic allergic contact dermatitis in response to repeated allergen exposure. J Immunol (2016) 197:4240-6. doi:10.4049/jimmunol.1600236
Galli SJ, Hammel I. Unequivocal delayed hypersensitivity in mast cell-deficient and beige mice. Science (1984) 226:710-3. doi:10.1126/science.6494907
Mekori YA, Galli SJ. Undiminished immunologic tolerance to contact sensitivity in mast cell-deficient W/Wv and Sl/Sld mice. J Immunol (1985) 135:879-85
Mekori YA, Chang JC, Wershil BK, Galli SJ. Studies of the role of mast cells in contact sensitivity responses. Passive transfer of the reaction into mast cell-deficient mice locally reconstituted with cultured mast cells: effect of reserpine on transfer of the reaction with DNP-specific cloned T cells. Cell Immunol (1987) 109:39-52
Abt MC, Artis D. The intestinal microbiota in health and disease: the influence of microbial products on immune cell homeostasis. Curr Opin Gastroenterol (2009) 25:496-502. doi:10.1097/MOG.0b013e328331b6b4
Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med (2012) 18:538-46. doi:10.1038/nm.2657
Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity (2012) 37(1):158-70. doi:10.1016/j.immuni.2012.04.011
Chervenick PA, Boggs DR. Decreased neutrophils and megakaryocytes in anemic mice of genotype W/Wv. J Cell Physiol (1969) 73:25-30. doi:10.1002/jcp.1040730104
Tsai M, Grimbaldeston MA, Yu M, Tam SY, Galli SJ. Using mast cell knock-in mice to analyze the roles of mast cells in allergic responses in vivo. Chem Immunol Allergy (2005) 87:179-97. doi:10.1159/000087644
Zhou JS, Xing W, Friend DS, Austen KF, Katz HR. Mast cell deficiency in Kit(W-sh)mice does not impair antibody-mediated arthritis. J Exp Med (2007) 204:2797-802. doi:10.1084/jem.20071391
Nigrovic PA, Gray DH, Jones T, Hallgren J, Kuo FC, Chaletzky B, et al. Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol (2008) 173:1693-701. doi:10.2353/ajpath.2008.080407
Manabe Y, Yoshimura M, Sakamaki K, Inoue A, Kakinoki A, Hokari S, et al. 1-Fluoro-2, 4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells. Eur J Immunol (2017) 47:60-7. doi:10.1002/eji.201646536
KalesnikoffJ, Huber M, Lam V, Damen JE, Zhang J, Siraganian RP, et al. Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity (2001) 14:801-11. doi:10.1016/S1074-7613(01)00159-5
Kitaura J, Song J, Tsai M, Asai K, Maeda-Yamamoto M, Mocsai A, et al. Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI. Proc Natl Acad Sci U S A (2003) 100:12911-6. doi:10.1073/pnas.1735525100
Kobayashi M, Nunomura S, Gon Y, Endo D, Kishiro S, Fukunaga M, et al. Abrogation of high-affinity IgE receptor-mediated mast cell activation at the effector phase prevents contact hypersensitivity to oxazolone. J Invest Dermatol (2010) 130:725-31. doi:10.1038/jid.2009.289
Piguet PF, Grau GE, Hauser C, Vassalli P. Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. J Exp Med (1991) 173:673-9. doi:10.1084/jem.173.3.673
Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature (1990) 346:274-6. doi:10.1038/346274a0
Kunder CA, St John AL, Li G, Leong KW, Berwin B, Staats HF, et al. Mast cell-derived particles deliver peripheral signals to remote lymph nodes. J Exp Med (2009) 206:2455-67. doi:10.1084/jem.20090805
Malaviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature (1996) 381:77-80. doi:10.1038/381077a0
Gordon JR, Galli SJ. Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha. J Exp Med (1994) 180:2027-37. doi:10.1084/jem.180.6.2027
Kakurai M, Monteforte R, Suto H, Tsai M, Nakae S, Galli SJ. Mast cell-derived tumor necrosis factor can promote nerve fiber elongation in the skin during contact hypersensitivity in mice. Am J Pathol (2006) 169:1713-21. doi:10.2353/ajpath.2006.060602
Ohtsu H, Kuramasu A, Tanaka S, Terui T, Hirasawa N, Hara M, et al. Plasma extravasation induced by dietary supplemented histamine in histamine-free mice. Eur J Immunol (2002) 32:1698-708. doi:10.1002/1521-4141(200206)32:6<1698::AID-IMMU1698>3.0.CO;2-7
Seike M, Furuya K, Omura M, Hamada-Watanabe K, Matsushita A, Ohtsu H. Histamine H(4) receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge. Allergy (2010) 65:319-26. doi:10.1111/j.1398-9995.2009.02240.x
Ohtsu H, Tanaka S, Terui T, Hori Y, Makabe-Kobayashi Y, Pejler G, et al. Mice lacking histidine decarboxylase exhibit abnormal mast cells. FEBS Lett (2001) 502:53-6. doi:10.1016/S0014-5793(01)02663-1
Wiener Z, Buzas E, Kovacs P, Csaba G, Szabo D, Kittel A, et al. Highly reduced peritoneal mast cell number and decreased c-kit expression in histidine decarboxylase knock out mice. Inflamm Res (2001) 50(Suppl 2):S55-6. doi:10.1007/pl00022406
Ghosh AK, Hirasawa N, Ohtsu H, Watanabe T, Ohuchi K. Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. J Exp Med (2002) 195:973-82. doi:10.1084/jem.20011782
Xu X, Zhang D, Zhang H, Wolters PJ, Killeen NP, Sullivan BM, et al. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia. J Exp Med (2006) 203:2907-17. doi:10.1084/jem.20061232
Dunn IS, Liberato DJ, Stampf JL, Castagnoli N Jr, Byers VS. Regulation of murine contact sensitivity to urushiol components by serum factors. J Invest Dermatol (1987) 89:296-8. doi:10.1111/1523-1747.ep12471534
Bruhns P, Jonsson F. Mouse and human FcR effector functions. Immunol Rev (2015) 268:25-51. doi:10.1111/imr.12350
Honda T, Miyachi Y, Kabashima K. Regulatory T cells in cutaneous immune responses. J Dermatol Sci (2011) 63:75-82. doi:10.1016/j.jdermsci.2011.06.004
Zielinski CE, Zuberbier T, Maurer M. Immunoregulation in cutaneous allergy: prevention and control. Curr Opin Allergy Clin Immunol (2012) 12:498-503. doi:10.1097/ACI.0b013e3283574ccb
Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity (2008) 29:771-81. doi:10.1016/j.immuni.2008.08.018