TNFreceptorsuperfamiljen

The TNF receptor superfamily (TNFRSF) comprises a large group of type I transmembrane receptors that bind ligands of the tumor necrosis factor (TNF) superfamily. Members regulate immune cell development, survival, differentiation, and death. Most TNFRSF members share extracellular cysteine-rich domains and intracellular motifs that determine signaling outcomes; several include a death domain that can recruit adaptor proteins to initiate apoptosis.

Upon ligand binding, many TNFRSF receptors form trimers or higher-order complexes, recruiting adaptor proteins such as TRADD, TRAF, RIP1, and FADD. Signaling activates transcription factors including NF-κB and AP-1 through canonical and noncanonical pathways, as well as MAP kinases. Receptors with death domains can initiate caspase cascades leading to programmed cell death or, conversely, promote survival signals that limit apoptosis in different contexts. The balance of these signals shapes immune responses and tissue homeostasis.

Functionally, TNFRSF signaling controls lymphoid organ development, B and T cell activation, dendritic cell function, and costimulation. Therapeutically important members include TNFR1 (TNFRSF1A) and TNFR2 (TNFRSF1B), CD40, OX40 (TNFRSF4), 4-1BB (TNFRSF9), GITR, RANK (TNFRSF11A), and Fas (CD95, TNFRSF6). Ligand interactions such as TNF-α/TNFR1, CD40L/CD40, and TRAIL/TRAIL receptors illustrate diverse outcomes from inflammatory signaling to cytotoxicity and tissue remodeling.

Clinically, TNFRSF pathways are implicated in cancer, autoimmunity, and infectious diseases. Therapeutic strategies include TNF inhibitors and receptor agonists or antagonists targeting specific receptors to modulate immune responses, bone metabolism, and apoptosis in disease contexts.