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Tumor necrosis factor-alpha (TNFA/TNFSF2) is amultifunctional cytokine that plays a key role in regulating inflammation, immune functions, host defense, and apoptosis (PMID: 16407280). TNFA signals through two distinct cell surface receptors, TNFR1 (TNFRSF1A, CD120a) and TNFR2 (TNFRSF1B, CD120b). TNFR1 is widely expressed, whereas TNFR2 exhibits more restricted expression, being found on CD4 and CD8 T lymphocytes, endothelial cells, microglia, oligodendrocytes, neuron subtypes, cardiac myocytes, thymocytes and human mesenchymal stem cells (PMID: 20489699; 22374304). In contrast to TNFR1, TNFR2 does not have a death domain. TNFR2 only signals for antiapoptotic reactions. However, recent evidence indicates that TNFR2 also signals to induce TRAF2 degradation (PMID: 22374304). Various defects in the TNFR2 pathway, due to polymorphisms in the TNFR2 gene, upregulated expression of TNFR2 and TNFR2 shedding, have been implicated in the pathology of several autoimmune disorders (PMID: 20489699).