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- Title
Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-gamma production in mice.
- Authors
Noubade, Rajkumar; Milligan, Graeme; Zachary, James F; Blankenhorn, Elizabeth P; del Rio, Roxana; Rincon, Mercedes; Teuscher, Cory
- Abstract
Histamine receptor H1 (H1R) is a susceptibility gene in both experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune orchitis (EAO), 2 classical T cell-mediated models of organ-specific autoimmune disease. Here we showed that expression of H1R in naive CD4+ T cells was required for maximal IFN-gamma production but was dispensable for proliferation. Moreover, H1R signaling at the time of TCR ligation was required for activation of p38 MAPK, a known regulator of IFN-gamma expression. Importantly, selective reexpression of H1R in CD4+ T cells fully complemented both the IFN-gamma production and the EAE susceptibility of H1R-deficient mice. These data suggest that the presence of H1R in CD4+ T cells and its interaction with histamine regulates early TCR signals that lead to Th1 differentiation and autoimmune disease.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 11, p3507
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI32792