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Transcription factor EGR2 controls homing and pathogenicity of TH17 cells in the central nervous system.
Gao, Yuanyuan; Wang, Yan; Chauss, Daniel; Villarino, Alejandro V; Link, Verena M; Nagashima, Hiroyuki; Spinner, Camille A; Koparde, Vishal N; Bouladoux, Nicolas; Abers, Michael S; Break, Timothy J; Chopp, Laura B; Park, Jung-Hyun; Zhu, Jinfang; Wiest, David L; Leonard, Warren J; Lionakis, Michail S; O'Shea, John J; Afzali, Behdad; Belkaid, Yasmine; Lazarevic, Vanja.
  • Gao Y; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Wang Y; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chauss D; Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Villarino AV; Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Link VM; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Nagashima H; Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Spinner CA; NIH Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Koparde VN; Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Bouladoux N; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Abers MS; CCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Break TJ; Advanced Biomedical Computational Sciences, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
  • Chopp LB; Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Park JH; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhu J; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Wiest DL; Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Leonard WJ; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Lionakis MS; Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • O'Shea JJ; Nuclear Dynamics and Cancer Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Afzali B; Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Belkaid Y; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lazarevic V; Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Immunol ; 24(8): 1331-1344, 2023 08.
Article en En | MEDLINE | ID: mdl-37443284
ABSTRACT
CD4+ T helper 17 (TH17) cells protect barrier tissues but also trigger autoimmunity. The mechanisms behind these opposing processes remain unclear. Here, we found that the transcription factor EGR2 controlled the transcriptional program of pathogenic TH17 cells in the central nervous system (CNS) but not that of protective TH17 cells at barrier sites. EGR2 was significantly elevated in myelin-reactive CD4+ T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. The EGR2 transcriptional program was intricately woven within the TH17 cell transcriptional regulatory network and showed high interconnectivity with core TH17 cell-specific transcription factors. Mechanistically, EGR2 enhanced TH17 cell differentiation and myeloid cell recruitment to the CNS by upregulating pathogenesis-associated genes and myelomonocytic chemokines. T cell-specific deletion of Egr2 attenuated neuroinflammation without compromising the host's ability to control infections. Our study shows that EGR2 regulates tissue-specific and disease-specific functions in pathogenic TH17 cells in the CNS.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Esclerosis Múltiple Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Esclerosis Múltiple Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article