Distinct roles of ORAI1 in T cell-mediated allergic airway inflammation and immunity to influenza A virus infection.

T cell activation and function depend on Ca 2+ signals mediated by store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T H 1) cell-mediated response to influenza A virus (IAV) infection and T H 2 cell-mediated allergic airway inflammation. T cell-specific deletion of Orai1 did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite-induced allergic airway inflammation. ORAI1 controlled the expression of genes including p53 and E2F transcription factors that regulate the cell cycle in T H 2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T H 2 cell function. Systemic application of a CRAC channel blocker suppressed allergic airway inflammation without compromising immunity to IAV infection, suggesting that inhibition of SOCE is a potential treatment for allergic airway disease.