Arthritis & rheumatology (Hoboken, N.J.) · 2021
Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.