CD317 stabilizes TNFR1 and confers the anti-inflammatory functions of MSCs via NF-κB/TSG6 pathway

• CD317 directly contributes to the immunosuppressive function of MSCs by stabilizing the TNFR1 complex, leading to hyper-activation of NF-κB and upregulation of TSG6. • The CD317/lipid-raft/TNFR1 complex is a novel mechanism through which MSCs exert anti-inflammatory effects in response to TNF-α. • CD317+ MSCs show enhanced therapeutic efficacy in mouse models of acute lung injury (ALI) and inflammatory bowel disease (IBD), addressing heterogeneity and inconsistency in MSC-based therapies. • This study provides a molecular basis for purifying homogenous MSC populations with enhanced anti-inflammatory functions, potentially improving clinical outcomes of MSC therapies.