Distinct roles of ORAI1 in T cell–mediated allergic airway inflammation and immunity to influenza A virus infection
Yin‐Hu Wang, Lucile Noyer, Sascha Kahlfuß, Dimitrius Raphael, Anthony Tao, Ulrike Kaufmann, Jingjie Zhu, Marisa Mitchell-Flack, Ikjot Sidhu, Fang Zhou, Martin Vaeth, Paul G. Thomas, Sean P. Saunders, Kenneth A. Stauderman, Maria A. Curotto de Lafaille, Stefan Feske
Abstract
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.