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Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-γ production in mice
Journal article   Open access   Peer reviewed

Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-γ production in mice

Rajkumar Noubade, Graeme Milligan, James F Zachary, Elizabeth P Blankenhorn, Roxana del Rio, Mercedes Rincon and Cory Teuscher
The Journal of clinical investigation, v 117(11), pp 3507-3518
01 Nov 2007
PMID: 17965772
url
https://doi.org/10.1172/JCI32792View
Published, Version of Record (VoR) Open

Abstract

Histamine receptor H 1 (H 1 R) 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 H 1 R in naive CD4 + T cells was required for maximal IFN-γ production but was dispensable for proliferation. Moreover, H 1 R signaling at the time of TCR ligation was required for activation of p38 MAPK, a known regulator of IFN-γ expression. Importantly, selective reexpression of H 1 R in CD4 + T cells fully complemented both the IFN-γ production and the EAE susceptibility of H 1 R-deficient mice. These data suggest that the presence of H 1 R in CD4 + T cells and its interaction with histamine regulates early TCR signals that lead to Th1 differentiation and autoimmune disease.

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Web of Science research areas
Medicine, Research & Experimental
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