Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis
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Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis. / Wang, Na; Wu, Weiju; Qiang, Cui; Ma, Ning; Wu, Kunyi; Liu, Dan; Wang, Jia Xing; Yang, Xiao; Xue, Li; Diao, Teng Yue; Liu, Jia Yu; Li, Ang; Zhang, Baojun; Li, Zong Fang; Farrar, Conrad A.; Banda, Nirmal K.; Bayarri-Olmos, Rafael; Garred, Peter; Zhou, Wuding; Li, Ke.
I: Arthritis and Rheumatology, Bind 73, Nr. 8, 2021, s. 1430-1440.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis
AU - Wang, Na
AU - Wu, Weiju
AU - Qiang, Cui
AU - Ma, Ning
AU - Wu, Kunyi
AU - Liu, Dan
AU - Wang, Jia Xing
AU - Yang, Xiao
AU - Xue, Li
AU - Diao, Teng Yue
AU - Liu, Jia Yu
AU - Li, Ang
AU - Zhang, Baojun
AU - Li, Zong Fang
AU - Farrar, Conrad A.
AU - Banda, Nirmal K.
AU - Bayarri-Olmos, Rafael
AU - Garred, Peter
AU - Zhou, Wuding
AU - Li, Ke
N1 - Publisher Copyright: © 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2021
Y1 - 2021
N2 - Objective: Collectin 11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. We undertook this study to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). Methods: A murine collagen-induced arthritis (CIA) model was used and combined two approaches, including gene deletion of Colec11 and treatment with recombinant CL-11 (rCL-11). Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines, and adaptive immune responses were assessed in mice with CIA. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen-presenting cell (APC) function. Serum CL-11 levels in RA patients were also examined. Results: Colec11−/− mice developed more severe arthritis than wild-type mice, as determined by disease incidence, clinical arthritis scores, and histopathology (P < 0.05). Disease severity was associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c+ cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacologic treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum CL-11 levels were lower in RA patients (n = 51) compared to healthy controls (n = 53). Reduction in serum CL-11 was inversely associated with the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and C-reactive protein level (P < 0.05). Conclusion: Our findings demonstrate a novel role of CL-11 in protection against RA, suggesting that the underlying mechanism involves suppression of APC activation and subsequent T cell responses.
AB - Objective: Collectin 11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. We undertook this study to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). Methods: A murine collagen-induced arthritis (CIA) model was used and combined two approaches, including gene deletion of Colec11 and treatment with recombinant CL-11 (rCL-11). Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines, and adaptive immune responses were assessed in mice with CIA. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen-presenting cell (APC) function. Serum CL-11 levels in RA patients were also examined. Results: Colec11−/− mice developed more severe arthritis than wild-type mice, as determined by disease incidence, clinical arthritis scores, and histopathology (P < 0.05). Disease severity was associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c+ cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacologic treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum CL-11 levels were lower in RA patients (n = 51) compared to healthy controls (n = 53). Reduction in serum CL-11 was inversely associated with the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and C-reactive protein level (P < 0.05). Conclusion: Our findings demonstrate a novel role of CL-11 in protection against RA, suggesting that the underlying mechanism involves suppression of APC activation and subsequent T cell responses.
U2 - 10.1002/art.41696
DO - 10.1002/art.41696
M3 - Journal article
C2 - 33605085
AN - SCOPUS:85109789147
VL - 73
SP - 1430
EP - 1440
JO - Arthritis & Rheumatology
JF - Arthritis & Rheumatology
SN - 2326-5205
IS - 8
ER -
ID: 302574815