Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis.
Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis.
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Collectin 11 在类风湿关节炎小鼠模型中的保护作用
DOI：
10.1002/art.41696
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Li K
中科院分区：
文献类型：
--
作者：
Wang N;Wu W;Qiang C;Ma N;Wu K;Liu D;Wang JX;Yang X;Xue L;Diao TY;Liu JY;Li A;Zhang B;Li ZF;Farrar CA;Banda NK;Bayarri-Olmos R;Garred P;Zhou W;Li K
凝集素 -11（CL -11）是一种可溶性C型凝集素，是先天免疫的介质。它在自身免疫性疾病中的作用尚不清楚。本研究的目的是确定CL -11在类风湿性关节炎（RA）小鼠模型中的作用。
采用了小鼠胶原诱导性关节炎（CIA）模型，结合Colec11基因缺失和重组（rCL -11）治疗方法。对CIA小鼠的关节炎症和组织破坏、炎性细胞因子的循环水平以及适应性免疫反应进行了评估。利用脾脏CD11c⁺细胞来检测CL -11对抗原呈递细胞（APC）功能的影响。还检测了RA患者的血清CL -11水平。
Colec11⁻/⁻小鼠比野生型（WT）小鼠发生更严重的关节炎（通过疾病发生率、临床关节炎评分和组织病理学确定；P < 0.05）。疾病严重程度与APC活化显著增强、Th1/Th17反应、致病性IgG2a产生和关节炎症以及炎性细胞因子循环水平升高有关。对CD11c⁺细胞的体外分析表明，CL -11对抑制APC活化和功能至关重要。用rCL -11对小鼠进行药物治疗可降低小鼠CIA的严重程度。对人血液样本的分析显示，RA患者（n = 51）的血清CL -11水平低于健康对照组（n = 53），血清CL -11降低还与DAS28、ESR和CRP呈负相关（P < 0.05）。
我们的研究结果表明CL -11在预防RA方面具有一种新的作用，提示其潜在机制涉及抑制APC活化以及随后的T细胞反应。
Collectin-11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. The goal of this study was to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). A murine collagen-induced arthritis (CIA) model, combining both gene deletion of Colec11 and recombinant (rCL-11) treatment approaches were employed. Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines and adaptive immune responses were assessed in CIA mice. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen presenting cell (APC) function. Serum levels of CL-11 in RA patients were also examined. Colec11−/− mice developed more severe arthritis than WT mice (as determined by disease incidence, clinical arthritis scores and histopathology; P<0.05). Disease severity is 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. Pharmacological treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum levels of CL-11 was lower in RA patients (n=51) compared to healthy controls (n=53), a serum CL-11 reduction also displays a negative relationship with DAS28, ESR and CRP (P<0.05). Our findings demonstrate a novel role for CL-11 in protection against RA, suggesting the underlying mechanism involved suppression of APC activation and subsequent T cell responses.
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