Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells
| Autor: | Lu Ni, Siyuan Wan, Xiaohu Wang, Xiao Ding, Anne Dejean, Chen Dong, Xiaohong Zhao |
|---|---|
| Přispěvatelé: | Tsinghua University [Beijing] (THU), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from the National Key Research and Development Program of China (2016YFC0906200 to C.D.), the National Natural Science Foundation of China (31630022, 31991173, 31821003, and 91642201 to C.D., 31570884 to X.W.), Beijing Municipal Commission of Science and Technology, China (Z181100001318007, Z181100006318015, and Z171100000417005 to C.D.), and Beijing Natural Science Foundation, China (5172017 to X.W.)., We thank all the Dong lab members for their help., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MESH: Body Temperature MESH: Th17 Cells Cellular differentiation SUMO protein Adaptive Immunity medicine.disease_cause SMAD4 Body Temperature Autoimmunity Mice 0302 clinical medicine Gene expression MESH: Smad4 Protein Immunology and Allergy MESH: Animals Smad4 Protein MESH: Cytokines MESH: Sumoylation Cell Differentiation MESH: Gene Expression Regulation 3. Good health Infectious Diseases 030220 oncology & carcinogenesis Cytokines MESH: Cell Differentiation MESH: Cell Nucleus Encephalomyelitis Autoimmune Experimental Fever Immunology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology 03 medical and health sciences heat shock response Immune system MESH: Fever medicine Animals autoimmune diseases Heat shock MESH: Encephalomyelitis Autoimmune Experimental MESH: Mice Transcription factor Cell Nucleus Autoimmune disease Sumoylation medicine.disease 030104 developmental biology Gene Expression Regulation MESH: Heat-Shock Response Th17 Cells MESH: Adaptive Immunity Heat-Shock Response |
| Zdroj: | Immunity Immunity, Elsevier, 2020, 52 (2), pp.328-341.e5. ⟨10.1016/j.immuni.2020.01.006⟩ Immunity, 2020, 52 (2), pp.328-341.e5. ⟨10.1016/j.immuni.2020.01.006⟩ |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2020.01.006 |
| Popis: | International audience; Fever, an evolutionarily conserved physiological response to infection, is also commonly associated with many autoimmune diseases, but its role in T cell differentiation and autoimmunity remains largely unclear. T helper 17 (Th17) cells are critical in host defense and autoinflammatory diseases, with distinct phenotypes and pathogenicity. Here, we show that febrile temperature selectively regulated Th17 cell differentiation in vitro in enhancing interleukin-17 (IL-17), IL-17F, and IL-22 expression. Th17 cells generated under febrile temperature (38.5°C-39.5°C), compared with those under 37°C, showed enhanced pathogenic gene expression with increased pro-inflammatory activities in vivo. Mechanistically, febrile temperature promoted SUMOylation of SMAD4 transcription factor to facilitate its nuclear localization; SMAD4 deficiency selectively abrogated the effects of febrile temperature on Th17 cell differentiation both in vitro and ameliorated an autoimmune disease model. Our results thus demonstrate a critical role of fever in shaping adaptive immune responses with implications in autoimmune diseases. |
| Databáze: | OpenAIRE |
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