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 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 (T 1) cell-mediated response t...

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Published in:Science advances 2022-10, Vol.8 (40), p.eabn6552-eabn6552
Main Authors: Wang, Yin-Hu, Noyer, Lucile, Kahlfuss, Sascha, Raphael, Dimitrius, Tao, Anthony Y, Kaufmann, Ulrike, Zhu, Jingjie, Mitchell-Flack, Marisa, Sidhu, Ikjot, Zhou, Fang, Vaeth, Martin, Thomas, Paul G, Saunders, Sean P, Stauderman, Kenneth, Curotto de Lafaille, Maria A, Feske, Stefan
Format: Article
Language:English
Subjects:
Allergens
Animals
Biomedicine and Life Sciences
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium Signaling
Cytokines - metabolism
E2F Transcription Factors
Health and Medicine
Inflammation
Influenza A virus
Mice
ORAI1 Protein - genetics
ORAI1 Protein - metabolism
SciAdv r-articles
Stromal Interaction Molecule 1 - metabolism
Transcription Factors - metabolism
Tumor Suppressor Protein p53 - metabolism
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Summary: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 (T 1) cell-mediated response to influenza A virus (IAV) infection and T 2 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 T 2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T 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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abn6552