Distinct Roles of ORAI1 in T Cell-mediated Allergic Airway Inflammation and Immunity to Influenza A Virus Infection

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Oct 7

PMID 36206339

Authors

Yin-Hu Wang

Lucile Noyer

Sascha Kahlfuss

Dimitrius Raphael

Anthony Y Tao

Ulrike Kaufmann

Jingjie Zhu

Marisa Mitchell-Flack

Ikjot Sidhu

Fang Zhou

Martin Vaeth

Paul G Thomas

Sean P Saunders

Kenneth Stauderman

Maria A Curotto de Lafaille

Stefan Feske

Affiliations

Soon will be listed here.

Abstract

T cell activation and function depend on Ca signals mediated by store-operated Ca entry (SOCE) through Ca release-activated Ca (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T1) cell-mediated response to influenza A virus (IAV) infection and T2 cell-mediated allergic airway inflammation. T cell-specific deletion of 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 T2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T2 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.

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