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Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells.
Chauss, Daniel; Freiwald, Tilo; McGregor, Reuben; Yan, Bingyu; Wang, Luopin; Nova-Lamperti, Estefania; Kumar, Dhaneshwar; Zhang, Zonghao; Teague, Heather; West, Erin E; Vannella, Kevin M; Ramos-Benitez, Marcos J; Bibby, Jack; Kelly, Audrey; Malik, Amna; Freeman, Alexandra F; Schwartz, Daniella M; Portilla, Didier; Chertow, Daniel S; John, Susan; Lavender, Paul; Kemper, Claudia; Lombardi, Giovanna; Mehta, Nehal N; Cooper, Nichola; Lionakis, Michail S; Laurence, Arian; Kazemian, Majid; Afzali, Behdad.
  • Chauss D; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
  • Freiwald T; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
  • McGregor R; Medic Clinic III, Department of Nephrology, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany.
  • Yan B; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
  • Wang L; Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
  • Nova-Lamperti E; Department of Biochemistry, Purdue University, West Lafayette, IN, USA.
  • Kumar D; Department of Computer Science, Purdue University, West Lafayette, IN, USA.
  • Zhang Z; Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepcion, Concepcion, Chile.
  • Teague H; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
  • West EE; Department of Computer Science, Purdue University, West Lafayette, IN, USA.
  • Vannella KM; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, USA.
  • Ramos-Benitez MJ; Laboratory of Inflammation & Cardiometabolic Diseases, Cardiovascular Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA.
  • Bibby J; Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA.
  • Kelly A; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
  • Malik A; Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Freeman AF; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
  • Schwartz DM; Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Portilla D; Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA.
  • Chertow DS; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
  • John S; Department of Medicine, Imperial College London, London, UK.
  • Lavender P; Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
  • Kemper C; Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
  • Lombardi G; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD, USA.
  • Mehta NN; Division of Nephrology and the Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, VA, USA.
  • Cooper N; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
  • Lionakis MS; Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Laurence A; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
  • Kazemian M; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
  • Afzali B; Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA.
Nat Immunol ; 23(1): 62-74, 2022 01.
Article in English | MEDLINE | ID: covidwho-1514418
ABSTRACT
The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vitamin D / Interferon-gamma / Interleukin-10 / Th1 Cells / SARS-CoV-2 Limits: Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-021-01080-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vitamin D / Interferon-gamma / Interleukin-10 / Th1 Cells / SARS-CoV-2 Limits: Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-021-01080-3