STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells
Abstract Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca2+ influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. We here identify patients with a novel mutation...
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201911592 |
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| author | Sascha Kahlfuss Ulrike Kaufmann Axel R Concepcion Lucile Noyer Dimitrius Raphael Martin Vaeth Jun Yang Priya Pancholi Mate Maus James Muller Lina Kozhaya Alireza Khodadadi‐Jamayran Zhengxi Sun Patrick Shaw Derya Unutmaz Peter B Stathopulos Cori Feist Scott B Cameron Stuart E Turvey Stefan Feske |
| author_facet | Sascha Kahlfuss Ulrike Kaufmann Axel R Concepcion Lucile Noyer Dimitrius Raphael Martin Vaeth Jun Yang Priya Pancholi Mate Maus James Muller Lina Kozhaya Alireza Khodadadi‐Jamayran Zhengxi Sun Patrick Shaw Derya Unutmaz Peter B Stathopulos Cori Feist Scott B Cameron Stuart E Turvey Stefan Feske |
| author_sort | Sascha Kahlfuss |
| collection | DOAJ |
| description | Abstract Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca2+ influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolished Ca2+ 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. |
| format | Article |
| id | doaj-art-5dea67d69b0a4240ad6b7dfd0ac39c79 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-5dea67d69b0a4240ad6b7dfd0ac39c792025-08-20T03:43:21ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-07-0112812510.15252/emmm.201911592STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cellsSascha Kahlfuss0Ulrike Kaufmann1Axel R Concepcion2Lucile Noyer3Dimitrius Raphael4Martin Vaeth5Jun Yang6Priya Pancholi7Mate Maus8James Muller9Lina Kozhaya10Alireza Khodadadi‐Jamayran11Zhengxi Sun12Patrick Shaw13Derya Unutmaz14Peter B Stathopulos15Cori Feist16Scott B Cameron17Stuart E Turvey18Stefan Feske19Department of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineThe Jackson Laboratory for Genomic MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineThe Jackson Laboratory for Genomic MedicineDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western UniversityDepartment of Obstetrics & Gynecology, Oregon Health & Science UniversityDivision of Allergy and Clinical Immunology, Department of Pediatrics, University of British ColumbiaDivision of Allergy and Clinical Immunology, Department of Pediatrics, University of British ColumbiaDepartment of Pathology, New York University Grossman School of MedicineAbstract Immunity to fungal infections is mediated by cells of the innate and adaptive immune system including Th17 cells. Ca2+ influx in immune cells is regulated by stromal interaction molecule 1 (STIM1) and its activation of the Ca2+ channel ORAI1. We here identify patients with a novel mutation in STIM1 (p.L374P) that abolished Ca2+ 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.https://doi.org/10.15252/emmm.201911592Ca2+ channelCandida albicansimmunodeficiencySTIM1Th17 cells |
| spellingShingle | Sascha Kahlfuss Ulrike Kaufmann Axel R Concepcion Lucile Noyer Dimitrius Raphael Martin Vaeth Jun Yang Priya Pancholi Mate Maus James Muller Lina Kozhaya Alireza Khodadadi‐Jamayran Zhengxi Sun Patrick Shaw Derya Unutmaz Peter B Stathopulos Cori Feist Scott B Cameron Stuart E Turvey Stefan Feske STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells EMBO Molecular Medicine Ca2+ channel Candida albicans immunodeficiency STIM1 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 | Ca2+ channel Candida albicans immunodeficiency STIM1 Th17 cells |
| url | https://doi.org/10.15252/emmm.201911592 |
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