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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yildirim, E; Carey, MA; Card, JW; Dietrich, A; Flake, GP; Zhang, Y; Bradbury, JA; Rebolloso, Y; Germolec, DR; Morgan, DL; Zeldin, DC; Birnbaumer, L

Published Date

  • September 15, 2012

Published In

Volume / Issue

  • 303 / 6

Start / End Page

  • L539 - L549

PubMed ID

  • 22797250

Pubmed Central ID

  • 22797250

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00389.2011

Language

  • eng

Conference Location

  • United States