TY - JOUR
T1 - CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines
AU - Takaki-Kuwahara, Ayako
AU - Arinobu, Yojiro
AU - Miyawaki, Kohta
AU - Yamada, Hisakata
AU - Tsuzuki, Hirofumi
AU - Irino, Kensuke
AU - Ayano, Masahiro
AU - Kimoto, Yasutaka
AU - Mitoma, Hiroki
AU - Akahoshi, Mitsuteru
AU - Tsukamoto, Hiroshi
AU - Horiuchi, Takahiko
AU - Niiro, Hiroaki
AU - Akashi, Koichi
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research(C) and a grant from the Japan Rheumatism Foundation.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/8/30
Y1 - 2019/8/30
N2 - Background: Recent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA). Methods: In a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients. Results: In the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001). Conclusion: CCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.
AB - Background: Recent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA). Methods: In a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients. Results: In the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001). Conclusion: CCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.
UR - http://www.scopus.com/inward/record.url?scp=85071684825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071684825&partnerID=8YFLogxK
U2 - 10.1186/s13075-019-1984-x
DO - 10.1186/s13075-019-1984-x
M3 - Article
C2 - 31470891
AN - SCOPUS:85071684825
VL - 21
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 1
M1 - 198
ER -