Journal
IMMUNITY
Volume 48, Issue 6, Pages 1220-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2018.04.009
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Funding
- Francis Crick Institute
- Cancer Research UK [FC001159]
- UK Medical Research Council [FC001159]
- Wellcome Trust [FC001159]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [16H06233, 17K19553, 16H06295]
- Core Research for Evolutional Science and Technology (CREST) program from the Japan Science and Technology Agency
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [17K19553, 16H06295, 16H06233] Funding Source: KAKEN
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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 GMCSF 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.
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