tetano
Editor, Senior Moderator
Sci Adv
. 2022 Oct 7;8(40):eabn6552.
doi: 10.1126/sciadv.abn6552. Epub 2022 Oct 7.
Distinct roles of ORAI1 in T cell-mediated allergic airway inflammation and immunity to influenza A virus infection
Yin-Hu Wang[SUP] 1 [/SUP], Lucile Noyer[SUP] 1 [/SUP], Sascha Kahlfuss[SUP] 1 [/SUP], Dimitrius Raphael[SUP] 1 [/SUP], Anthony Y Tao[SUP] 1 [/SUP], Ulrike Kaufmann[SUP] 1 [/SUP], Jingjie Zhu[SUP] 1 [/SUP], Marisa Mitchell-Flack[SUP] 1 [/SUP], Ikjot Sidhu[SUP] 1 [/SUP], Fang Zhou[SUP] 1 [/SUP], Martin Vaeth[SUP] 1 [/SUP], Paul G Thomas[SUP] 2 [/SUP], Sean P Saunders[SUP] 3 [/SUP], Kenneth Stauderman[SUP] 4 [/SUP], Maria A Curotto de Lafaille[SUP] 3 [/SUP], Stefan Feske[SUP] 1 [/SUP]
Affiliations
Abstract
T cell activation and function depend on Ca[SUP]2+[/SUP] signals mediated by store-operated Ca[SUP]2+[/SUP] entry (SOCE) through Ca[SUP]2+[/SUP] release-activated Ca[SUP]2+[/SUP] (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T[SUB]H[/SUB]1) cell-mediated response to influenza A virus (IAV) infection and T[SUB]H[/SUB]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[SUB]H[/SUB]2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T[SUB]H[/SUB]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.
. 2022 Oct 7;8(40):eabn6552.
doi: 10.1126/sciadv.abn6552. Epub 2022 Oct 7.
Distinct roles of ORAI1 in T cell-mediated allergic airway inflammation and immunity to influenza A virus infection
Yin-Hu Wang[SUP] 1 [/SUP], Lucile Noyer[SUP] 1 [/SUP], Sascha Kahlfuss[SUP] 1 [/SUP], Dimitrius Raphael[SUP] 1 [/SUP], Anthony Y Tao[SUP] 1 [/SUP], Ulrike Kaufmann[SUP] 1 [/SUP], Jingjie Zhu[SUP] 1 [/SUP], Marisa Mitchell-Flack[SUP] 1 [/SUP], Ikjot Sidhu[SUP] 1 [/SUP], Fang Zhou[SUP] 1 [/SUP], Martin Vaeth[SUP] 1 [/SUP], Paul G Thomas[SUP] 2 [/SUP], Sean P Saunders[SUP] 3 [/SUP], Kenneth Stauderman[SUP] 4 [/SUP], Maria A Curotto de Lafaille[SUP] 3 [/SUP], Stefan Feske[SUP] 1 [/SUP]
Affiliations
- PMID: 36206339
- DOI: 10.1126/sciadv.abn6552
Abstract
T cell activation and function depend on Ca[SUP]2+[/SUP] signals mediated by store-operated Ca[SUP]2+[/SUP] entry (SOCE) through Ca[SUP]2+[/SUP] release-activated Ca[SUP]2+[/SUP] (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T[SUB]H[/SUB]1) cell-mediated response to influenza A virus (IAV) infection and T[SUB]H[/SUB]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[SUB]H[/SUB]2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T[SUB]H[/SUB]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.