TNFSF8

TNFSF8 encodes the CD30 ligand (CD30L), a member of the tumor necrosis factor (TNF) ligand superfamily. It is a type II transmembrane protein that forms homotrimers and can be proteolytically cleaved to release a soluble form (sCD30L). CD30L interacts with its receptor CD30 (TNFRSF8) on activated lymphocytes, shaping immune responses.

Expression pattern: CD30L is expressed predominantly by activated CD4+ and CD8+ T cells, B cells, natural killer cells, eosinophils, and dendritic cells under certain conditions. Expression is upregulated upon immune activation and inflammation.

Function: Engagement of CD30L with CD30 promotes T cell activation and proliferation, enhances B cell growth, and supports immunoglobulin production and class switching. The CD30-CD30L axis participates in germinal center reactions and Th2-biased responses; it can provide costimulatory signals that influence cytokine production.

Regulation and signaling: CD30L signaling through CD30 activates NF-κB and MAPK pathways, influencing cell survival and cytokine production. The soluble form can act at a distance, modulating immune responses; shedding is mediated by metalloproteases such as ADAM family proteases.

Clinical relevance: Abnormal CD30–CD30L signaling is associated with Hodgkin lymphoma, anaplastic large cell lymphoma, and other inflammatory conditions. CD30L expression and soluble CD30L levels have been studied as biomarkers; targeting the axis has been explored for therapeutic applications, including monoclonal antibodies and ligand-targeted approaches.