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

Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L539-49. doi: 10.1152/ajplung.00389.2011. Epub 2012 Jul 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / immunology
  • Animals
  • Bronchial Hyperreactivity / immunology*
  • Female
  • Interleukin-2
  • Lung / immunology*
  • Male
  • Mice
  • Signal Transduction / immunology
  • Spleen / cytology
  • TRPC Cation Channels / deficiency
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / physiology*
  • Th2 Cells / immunology*


  • Allergens
  • Interleukin-2
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1