Soluble Fas ligand drives autoantibody-induced arthritis by binding to DR5/TRAIL-R2.

ABSTRACT: To date, no study has demonstrated that soluble Fas ligand (sFasL)-mediated inflammation is regulated via interaction with Fas in vivo. We found that FasL interacts specifically with tumor necrosis factor receptor superfamily (TNFRSF)10B, also known as death receptor (DR)5. Autoantibody-induced arthritis (AIA) was attenuated in FasL (Fasl^gld/gld)- and soluble FasL (Fasl^Δs/Δs)-deficient mice, but not in Fas (Fas^lpr/lpr and Fas^-/-)- or membrane FasL (Fasl^Δm/Δm)-deficient mice, suggesting sFasL promotes inflammation by binding to a Fas-independent receptor. Affinity purification mass spectrometry analysis using human (h) fibroblast-like synovial cells (FLSCs) identified DR5 as one of several proteins tha

SUBMITTER: Jeong D 

PROVIDER: S-EPMC8257255 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature