CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines

Ayako Takaki-Kuwahara, Yojiro Arinobu, Kohta Miyawaki, Hisakata Yamada, Hirofumi Tsuzuki, Kensuke Irino, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Hiroshi Tsukamoto, Takahiko Horiuchi, Hiroaki Niiro, Koichi Akashi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number198
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - Aug 30 2019

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Rheumatoid Arthritis
Joints
Lymphocytes
Cytokines
Synovial Fluid
Experimental Arthritis
Interleukin-17
Inflammation
CC Chemokines
Autoimmune Diseases
Arthritis
Flow Cytometry
Chronic Disease
Cell Count
Lymph Nodes
Ligands
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines. / Takaki-Kuwahara, Ayako; Arinobu, Yojiro; Miyawaki, Kohta; Yamada, Hisakata; Tsuzuki, Hirofumi; Irino, Kensuke; Ayano, Masahiro; Kimoto, Yasutaka; Mitoma, Hiroki; Akahoshi, Mitsuteru; Tsukamoto, Hiroshi; Horiuchi, Takahiko; Niiro, Hiroaki; Akashi, Koichi.

In: Arthritis Research and Therapy, Vol. 21, No. 1, 198, 30.08.2019.

Research output: Contribution to journalArticle

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abstract = "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.",
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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

PY - 2019/8/30

Y1 - 2019/8/30

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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.

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