Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis

Abstract

Objective 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). Methods 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. Results Colec11^‐/‐ mice developed more severe arthritis than WT mice (as determined by disease incidence, clinical arthritis scores and histopathology; P+ 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). Conclusion 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.