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

Noubade, R., Milligan, G. , Zachary, J.F., Blankenhorn, E.P., del Rio, R., Rincorn, M. and Teuscher, C. (2007) Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-γ production in mice. Journal of Clinical Investigation, 117(11), pp. 3507-3518.

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-γ 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-γ expression. Importantly, selective reexpression of H1R in CD4⁺ T cells fully complemented both the IFN-γ 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milligan, Professor Graeme
• Authors: Noubade, R., Milligan, G., Zachary, J.F., Blankenhorn, E.P., del Rio, R., Rincorn, M., and Teuscher, C.
• Subjects: Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Journal of Clinical Investigation
• Publisher: Americal Society for Clinical Investigation
• ISSN: 0021-9738