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

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;...

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Published inAmerican journal of physiology. Lung cellular and molecular physiology Vol. 303; no. 6; pp. L539 - L549
Main Authors Yildirim, Eda, Carey, Michelle A, Card, Jeffrey W, Dietrich, Alexander, Flake, Gordon P, Zhang, Yingpei, Bradbury, J Alyce, Rebolloso, Yvette, Germolec, Dori R, Morgan, Daniel L, Zeldin, Darryl C, Birnbaumer, Lutz
Format Journal Article
LanguageEnglish
Published United States American Physiological Society 15.09.2012
Subjects
Allergens - immunology
Animals
Asthma
Autoimmune diseases
Bronchial Hyperreactivity - immunology
Cells
Female
Interleukin-2
Lung - immunology
Lungs
Male
Mice
Pathology
Physiology
Signal Transduction - immunology
Spleen - cytology
T cell receptors
Th2 Cells - immunology
TRPC Cation Channels - deficiency
TRPC Cation Channels - genetics
TRPC Cation Channels - physiology
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Summary: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.
Bibliography:E. Yildirim and M. A. Carey contributed equally to this work.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00389.2011