Abstract

Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs-naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair-associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.