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10.1016/j.immuni.2018.04.009

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C6024031!6024031 !29802020
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suck abstract from ncbi


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pmid29802020
      Immunity 2018 ; 48 (6 ): 1220-1232.e5
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  • Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis #MMPMID29802020
  • Hirota K ; Hashimoto M ; Ito Y ; Matsuura M ; Ito H ; Tanaka M ; Watanabe H ; Kondoh G ; Tanaka A ; Yasuda K ; Kopf M ; Potocnik AJ ; Stockinger B ; Sakaguchi N ; Sakaguchi S
  • Immunity 2018[Jun]; 48 (6 ): 1220-1232.e5 PMID29802020 show ga
  • Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention.
  • |Animals [MESH]
  • |Arthritis, Rheumatoid/*immunology/metabolism [MESH]
  • |Autoimmune Diseases/immunology/metabolism [MESH]
  • |Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis/*immunology [MESH]
  • |Humans [MESH]
  • |Lymphocytes/*immunology/metabolism [MESH]
  • |Mice [MESH]
  • |Stromal Cells/*immunology/metabolism [MESH]
  • |Synovial Membrane/immunology/metabolism [MESH]


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