title: Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function.
abstract: Mast cells (MCs) play an important role in the regulation of protective adaptive immune responses against pathogens. However, it is still unclear whether MCs promote such host defense responses via direct effects on T cells or rather by modifying the functions of antigen-presenting cells. To identify the underlying mechanisms of the immunoregulatory capacity of MCs, we investigated the impact of MCs on dendritic cell (DC) maturation and function. We found that murine peritoneal MCs underwent direct crosstalk with immature DCs that induced DC maturation as evidenced by enhanced expression of costimulatory molecules. Furthermore, the MC/DC interaction resulted in the release of the T-cell modulating cytokines IFN-γ, IL-2, IL-6 and TGF-β into coculture supernatants and increased the IL-12p70, IFN-γ, IL-6 and TGF-β secretion of LPS-matured DCs. Such MC-"primed" DCs subsequently induced efficient CD4+ T-cell proliferation. Surprisingly, we observed that MC-primed DCs stimulated CD4+ T cells to release high levels of IFN-γ and IL-17, demonstrating that MCs promote Th1 and Th17 responses. Confirming our in vitro findings, we found that the enhanced disease progression of MC-deficient mice in Leishmania major infection is correlated with impaired induction of both Th1 and Th17 cells.
authors.affiliation: Institute for Immunology, University of Technology Dresden, Medical Faculty Carl-Gustav Carus, Dresden, Germany. anne.dudeck@tu-dresden.de
authors.forename: Anne
authors.initials: A
authors.lastname: Dudeck
authors.forename: Cathleen A
authors.initials: CA
authors.lastname: Suender
authors.forename: Susanna Lopez
authors.initials: SL
authors.lastname: Kostka
authors.forename: Esther
authors.initials: E
authors.lastname: von Stebut
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002450:Cell Communication; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology; D018450:Disease Progression; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D007375:Interleukin-1; D020381:Interleukin-17; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma