Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis

Open access
Date
2018-06-19Type
- Journal Article
Citations
Cited 101 times in
Web of Science
Cited 108 times in
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ETH Bibliography
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Abstract
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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000271845Publication status
publishedExternal links
Journal / series
ImmunityVolume
Pages / Article No.
Publisher
ElsevierSubject
GM-CSF; Th17; IL-17; ILCs; innate lymphoid cells; autoimmunity; arthritis; SKGOrganisational unit
03596 - Kopf, Manfred / Kopf, Manfred
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Show all metadata
Citations
Cited 101 times in
Web of Science
Cited 108 times in
Scopus
ETH Bibliography
yes
Altmetrics