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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Immunity
2018 ; 48
(6
): 1220-1232.e5
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gab.com Text
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English Wikipedia
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.