Open AccessSTIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
Author(s) -
Kahlfuss Sascha,
Kaufmann Ulrike,
Concepcion Axel R,
Noyer Lucile,
Raphael Dimitrius,
Vaeth Martin,
Yang Jun,
Pancholi Priya,
Maus Mate,
Muller James,
Kozhaya Lina,
KhodadadiJamayran Alireza,
Sun Zhengxi,
Shaw Patrick,
Unutmaz Derya,
Stathopulos Peter B,
Feist Cori,
Cameron Scott B,
Turvey Stuart E,
Feske Stefan
Publication year - 2020
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201911592
Subject(s) - grossman , library science , medicine , gerontology , computer science , economics , keynesian economics
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 ( STIM 1) and its activation of the Ca 2+ channel ORAI 1. We here identify patients with a novel mutation in STIM 1 (p.L374P) that abolished Ca 2+ influx and resulted in increased susceptibility to fungal and other infections. In mice, deletion of STIM 1 in all immune cells enhanced susceptibility to mucosal C. albicans infection, whereas T cell‐specific deletion of STIM 1 impaired immunity to systemic C. albicans infection. STIM 1 deletion impaired the production of Th17 cytokines essential for antifungal immunity and compromised the expression of genes in several metabolic pathways including Foxo and HIF 1α signaling that regulate glycolysis and oxidative phosphorylation ( OXPHOS ). Our study further revealed distinct roles of STIM 1 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.