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STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells

Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca(2+) influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca(2+) channel ORAI1. We here identify patients with a novel mutation in ST...

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Autores principales: Kahlfuss, Sascha, Kaufmann, Ulrike, Concepcion, Axel R, Noyer, Lucile, Raphael, Dimitrius, Vaeth, Martin, Yang, Jun, Pancholi, Priya, Maus, Mate, Muller, James, Kozhaya, Lina, Khodadadi‐Jamayran, Alireza, Sun, Zhengxi, Shaw, Patrick, Unutmaz, Derya, Stathopulos, Peter B, Feist, Cori, Cameron, Scott B, Turvey, Stuart E, Feske, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411566/
https://www.ncbi.nlm.nih.gov/pubmed/32609955
http://dx.doi.org/10.15252/emmm.201911592
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author Kahlfuss, Sascha
Kaufmann, Ulrike
Concepcion, Axel R
Noyer, Lucile
Raphael, Dimitrius
Vaeth, Martin
Yang, Jun
Pancholi, Priya
Maus, Mate
Muller, James
Kozhaya, Lina
Khodadadi‐Jamayran, Alireza
Sun, Zhengxi
Shaw, Patrick
Unutmaz, Derya
Stathopulos, Peter B
Feist, Cori
Cameron, Scott B
Turvey, Stuart E
Feske, Stefan
author_facet Kahlfuss, Sascha
Kaufmann, Ulrike
Concepcion, Axel R
Noyer, Lucile
Raphael, Dimitrius
Vaeth, Martin
Yang, Jun
Pancholi, Priya
Maus, Mate
Muller, James
Kozhaya, Lina
Khodadadi‐Jamayran, Alireza
Sun, Zhengxi
Shaw, Patrick
Unutmaz, Derya
Stathopulos, Peter B
Feist, Cori
Cameron, Scott B
Turvey, Stuart E
Feske, Stefan
author_sort Kahlfuss, Sascha
collection PubMed
description Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca(2+) influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca(2+) channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolished Ca(2+) influx and resulted in increased susceptibility to fungal and other infections. In mice, deletion of STIM1 in all immune cells enhanced susceptibility to mucosal C. albicans infection, whereas T cell‐specific deletion of STIM1 impaired immunity to systemic C. albicans infection. STIM1 deletion impaired the production of Th17 cytokines essential for antifungal immunity and compromised the expression of genes in several metabolic pathways including Foxo and HIF1α signaling that regulate glycolysis and oxidative phosphorylation (OXPHOS). Our study further revealed distinct roles of STIM1 in regulating transcription and metabolic programs in non‐pathogenic Th17 cells compared to pathogenic, proinflammatory Th17 cells, a finding that may potentially be exploited for the treatment of Th17 cell‐mediated inflammatory diseases.
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spelling pubmed-74115662020-08-10 STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells Kahlfuss, Sascha Kaufmann, Ulrike Concepcion, Axel R Noyer, Lucile Raphael, Dimitrius Vaeth, Martin Yang, Jun Pancholi, Priya Maus, Mate Muller, James Kozhaya, Lina Khodadadi‐Jamayran, Alireza Sun, Zhengxi Shaw, Patrick Unutmaz, Derya Stathopulos, Peter B Feist, Cori Cameron, Scott B Turvey, Stuart E Feske, Stefan EMBO Mol Med Articles Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca(2+) influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca(2+) channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolished Ca(2+) influx and resulted in increased susceptibility to fungal and other infections. In mice, deletion of STIM1 in all immune cells enhanced susceptibility to mucosal C. albicans infection, whereas T cell‐specific deletion of STIM1 impaired immunity to systemic C. albicans infection. STIM1 deletion impaired the production of Th17 cytokines essential for antifungal immunity and compromised the expression of genes in several metabolic pathways including Foxo and HIF1α signaling that regulate glycolysis and oxidative phosphorylation (OXPHOS). Our study further revealed distinct roles of STIM1 in regulating transcription and metabolic programs in non‐pathogenic Th17 cells compared to pathogenic, proinflammatory Th17 cells, a finding that may potentially be exploited for the treatment of Th17 cell‐mediated inflammatory diseases. John Wiley and Sons Inc. 2020-07-01 2020-08-07 /pmc/articles/PMC7411566/ /pubmed/32609955 http://dx.doi.org/10.15252/emmm.201911592 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Kahlfuss, Sascha
Kaufmann, Ulrike
Concepcion, Axel R
Noyer, Lucile
Raphael, Dimitrius
Vaeth, Martin
Yang, Jun
Pancholi, Priya
Maus, Mate
Muller, James
Kozhaya, Lina
Khodadadi‐Jamayran, Alireza
Sun, Zhengxi
Shaw, Patrick
Unutmaz, Derya
Stathopulos, Peter B
Feist, Cori
Cameron, Scott B
Turvey, Stuart E
Feske, Stefan
STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title_full STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title_fullStr STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title_full_unstemmed STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title_short STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
title_sort stim1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic th17 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411566/
https://www.ncbi.nlm.nih.gov/pubmed/32609955
http://dx.doi.org/10.15252/emmm.201911592
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