| First Author | Wang N | Year | 2021 |
| Journal | Arthritis Rheumatol | Volume | 73 |
| Issue | 8 | Pages | 1430-1440 |
| PubMed ID | 33605085 | Mgi Jnum | J:361469 |
| Mgi Id | MGI:7857024 | Doi | 10.1002/art.41696 |
| Citation | Wang N, et al. (2021) Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis. Arthritis Rheumatol 73(8):1430-1440 |
| abstractText | 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. |
