Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: Severely blunted allergen-induced pulmonary Th2 cell response and lung hyperresponsiveness in type 1 transient receptor potential channel-deficient mice.

Authors: Eda Yildirim, Michelle A Carey, Jeffrey W Card, Alexander Dietrich, Gordon P Flake, Yingpei Zhang, J Alyce Bradbury, Yvette Rebolloso, Dori R Germolec, Daniel L Morgan, Darryl C Zeldin, Lutz Birnbaumer

Journal, date & volume: Am. J. Physiol. Lung Cell Mol. Physiol., 2012 Sep 15 , 303, L539-49

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22797250

Abstract
Transient receptor potential channels (TRPCs) are widely expressed and regulate Ca²⁺ entry in the cells that participate in the pathophysiology of airway hyperreactivity, inflammation, and remodeling. In vitro studies point to a role for TRPC1-mediated Ca²⁺ signaling in several of these cell types; however, physiological evidence is lacking. Here we identify TRPC1 signaling as proinflammatory and a regulator of lung hyperresponsiveness during allergen-induced pulmonary response. TRPC1-deficient (Trpc1(-/-)) mice are hyposensitive to methacholine challenge and have significantly reduced allergen-induced pulmonary leukocyte infiltration coupled with an attenuated T helper type 2 (Th2) cell response. Upon in vitro allergen exposure, Trpc1(-/-) splenocytes show impaired proliferation and T cell receptor-induced IL-2 production. A high number of germinal centers in spleens of Trpc1(-/-) mice and elevated levels of immunoglobulins in their serum are indicative of dysregulated B cell function and homeostasis. Thus we propose that TRPC1 signaling is necessary in lymphocyte biology and in regulation of allergen-induced lung hyperresponsiveness, making TRPC1 a potential target for treatment of immune diseases and asthma.