SAT0001 Mechanism and significance of complement c3 receptor in collagen-induced rheumatoid arthritis mice model
Authors: L. Dan, L. ke
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease, mainly manifested as small joint synovitis. Disease progression appears joint swelling, bone and cartilage damage, deformity and activity limited. The etiology of RA is still unclear and is generally considered to be an immune-mediated inflammatory disease. The activation pathway and regulation function of the complement system have become the hotspot of the research of RA pathogenesis. Previous studies have found that C3-/- mice had lower levels of antibodies to collagen in the Type II collagen-induced rheumatoid arthritis (CIA model), and the molecular mechanism is unclear. The small fragment C3a and large segment iC3b produced by C3 activation are the main effect products, and their biological effects are performed by combining with the specific receptor, C3aR and CD11b respectively. <h3>Objectives</h3> To investigate the mechanism of C3a and C3b, the cleavage products of complement C3 in rheumatoid arthritis, binding to their corresponding receptors, the signalling pathway of complement activation and the effect on arthritic conditions. <h3>Methods</h3> This study was intended to establish a CIA model on C3aR knockout and CR3 knockout mice (C3aR-/-or CD11b-/-) to investigate the effect of complement C3a-C3aR signalling and iC3b-CR3 signalling on rheumatoid arthritis. Methods using C57BL/6 background transgenic mice (Gifted by King's College London), Mice were divided into 3 groups according to the experimental mouse strains: C3aR-/- group, CD11b-/- group and WT control group. The clinical score of the joints in each group was measured after the establishment of the CIA model through collagen induction. Moreover, joint specimens were collected for pathologic grading. Besides, the level of CD4 +T cell, CD8 +T cell, Th17/Treg ratio and the level of IFN-gamma of NK cell in mouse spleen were detected by flow cytometry. <h3>Results</h3> 1. The clinical score of C3aR-/- group was slightly lower than that of WT group, and the clinical score of CD11b-/- group was significantly higher than that of WT group; 2. Pathological score (12 points): The CIA scores of CD11b-/- group, C3aR-/- group and WT group were 9.35±0.75, 4.81±0.63 and 5.85±0.55 respectively. The CIA scores of CD11b-/- group was significantly higher than that of WT group, which were consistent with clinical score; 3.Through the flow cytometry detection, compared with the WT group, CD4 +T cell, CD8 +T cell and Th17 percentage increased significantly, and Treg cell decreased. In addition, the secretion of IFN-gamma of Splenic NK cell was significantly reduced. <h3>Conclusions</h3> iC3b as well as C3a could bind to their respective complement receptor, and express different influence in the immune mechanism of RA, The iC3b-CD11b signalling has a protective effect in RA, while the C3a-C3aR signalling has an inflammatory aggravation effect. Through this study, it helps us to invent the drug related to complement components and their receptors, and further be used in the clinical treatment of RA. <h3>Disclosure of Interest</h3> None declared