CARD 11 blockade suppresses murine collagen‐induced arthritis via inhibiting CARD 11/ B cl10 assembly and T helper type 17 response

Summary The scaffold protein caspase recruitment domain‐containing protein 11 ( CARD 11) is implicated in the regulation of inflammation and autoimmunity. The present study aimed to explore the role of CARD 11 in the pathogenesis of rheumatoid arthritis ( RA ). Mice with collagen‐induced arthritis ( CIA ) were treated with either CARD 11‐targeted interfering RNA ( CARD 11 siRNA ) or control siRNA by intraperitoneal injection every 3 days after CIA establishment. The clinical score of arthritis was recorded every other day. Synovial inflammation and cartilage erosion were evaluated by histology and microcomputed tomography (micro‐ CT ). Serum anti‐type II collagen (anti‐ CII ) antibodies and cytokines were measured by enzyme‐linked immunosorbent assay ( ELISA ). The CARD 11/ B cl10 formation and nuclear factor‐kappa B ( NF ‐ κB ) activation was assessed by immunoprecipitation and immunoblotting, and the percentage of T helper type 17 ( T h17) cells was determined by flow cytometry. Systemic administration of CARD 11 siRNA significantly reduced the clinical score of CIA severity. As indicated by the histology, joint inflammation and destruction were attenuated by CARD 11 siRNA treatment. Micro‐ CT demonstrated less severe joint destruction in CARD 11 siRNA ‐treated mice than in control mice. CARD 11 siRNA treatment resulted in inhibition of CARD 11/ B cl10 formation and the subsequent NF ‐ κB activation. In addition, treatment with CARD 11 siRNA resulted in a pronounced decrease in proinflammatory cytokines interleukin ( IL) ‐1β, IL ‐6 and IL ‐17. Serum anti‐ CII antibody and the percentage of T h17 cells were also significantly reduced. CARD 11 is involved in the pathogenesis of CIA by formation of the CARD 11/ B cl10 complex and enhancement of the T h17 cell response. Targeting CARD 11 provides a novel research direction in the development of therapeutic strategies for RA .