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Histamine enhances TGF‐β1‐mediated suppression of Th2 responses
Author(s) -
KUNZMANN S.,
MANTEL P.-Y.,
WOHLFAHRT J. G.,
AKDIS M.,
BLASER K.,
SCHMIDT-WEBER C. B.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1008com
Subject(s) - histamine , chemistry , histamine h2 receptor , histamine h4 receptor , transforming growth factor , histamine h1 receptor , cytokine , histamine receptor , receptor , immune system , microbiology and biotechnology , immunology , biology , endocrinology , biochemistry , antagonist
Susceptibility of T cells to TGF‐β1 produced by regulatory T cells has an important impact on the induction and maintenance of peripheral tolerance and therefore on the development of autoimmunity, cancer, and allergy. Histamine not only mediates the deleterious effects of allergic reactions, it can also modulate the Th1/Th2 cell balance. We demonstrate that histamine dose‐dependently enhanced TGF‐β1‐mediated suppression and TGF‐β1 responsiveness of CD4 + T cells. This effect was mediated by the histamine 2 receptor (H2R), as demonstrated by receptor‐specific agonists and antagonists. Furthermore, the histamine effect on TGF‐β1 responsiveness was cAMP/PKA dependent. This pathway is activated by the H2R, which is preferentially expressed on Th2 cells. Thus a higher additive effect of histamine on TGF‐β1 responsiveness was found in Th2 cells compared with Th1 cells. In fact, findings are confirmed by analysis of cytokine regulation, since activation of the H2R/cAMP pathway promoted TGF‐β1‐mediated IL‐4 inhibition but was ineffective in suppressing IFN‐γ. These results demonstrate that histamine supports TGF‐β1 susceptibility of T cells. Moreover, Th2 cells are more affected by histamine‐enhanced TGF‐β1 suppression, which is particularly important for the regulation of allergen‐specific T cells in allergic immune responses.—S. Kunzmann, P.‐Y. Mantel, J. G. Wohlfahrt, M. Akdis, K. Blaser, C. B. Schmidt‐Weber, FASEB J. 17, 1089–1095 (2003)