UC San Diego
The role of TRPV1 channels on CD4+ T-cells activation
- Author(s): To, Tak Kin
- et al.
TRPV1 is a non-selective ion channel best studied in peripheral sensory neurons as a pain receptor. Here we demonstrate the functional expression of TRPV1 by CD4⁺ T cells and its physiological consequences. TRPV1 is activated downstream of PLC-[gamma]1 upon TCR ligation and acts as a non-store operated Ca2⁺- channel. CD4⁺ T cell development, differentiation and survival are intact in Trpv1-/- mice. In contrast, TRPV1-mediated Ca2⁺ influx is required for the proper transduction of the major TCR- mediated signaling events and for the subsequent cytokine production. Mouse CD4⁺ T cells treated with pharmacological TRPV1 antagonists display similar phenotype of Trpv1-/- CD4⁺ T cells. In vivo, Trpv1-/- naïve CD4⁺ T cells adoptively transferred to Rag1-/- recipients failed to acquire inflammatory properties and did not provoke colitis. Thus, TRPV1 has an indispensible role in CD4⁺ T cell activation and its inhibition might be implemented to restrain pathogenic CD4⁺ T cell responses