The tumor necrosis factor receptor superfamily (TNFRSF) is characterized by the ability to bind tumor necrosis factor superfamily (TNFSF) ligands
[25][28]. The TNFRSF comprises 29 receptors, including TNFR1 and TNFR2 and the TNFSF comprises 19 ligands
[25][29]. TNFR1 is expressed on almost all cells
[30] and has extracellular TNF-binding structures characterized by four repeated cysteine-rich domains (CRDs: CRD1, CRD2, CRD3, and CRD4)
[31][32]. TNFR1 exists in its trimetric form before stimulation by TNF-α. Monomeric TNF receptors typically trimerize around TNF ligands that recruit TNF receptor-associated factors (TRAF) to the membrane and initiate a downstream signaling cascade
[33][34]. TNFR1 has a cytoplasmic region, designated as the death domain (DD), which initiates a cytotoxic signal
[35]. TNFR1 activation of NF-κB is dependent on several molecules such as the receptor-interacting protein kinase 1 (RIPK1, also known as RIP1), TNFR1-associated death domain (TRADD), TRAF2, and Fas-associated death domain (FADD)
[36]. TNFR1 activates various responses. For example, TNFR1 promotes inflammatory responses, regulates cytokines, chemokines, adhesion molecules and other receptors, as well as induces the migration of neutrophils, and regulates the complement system
[25]. The interaction of TNF-α and TNFRs is significantly involved in the development of lymphatic tissue; TNFR1-deficient mice show reduced numbers of Peyer’s patches and exhibit distressed germinal center formation in the white pulp of the spleen and follicular dendritic cell development and localization. TNFR1 is the likely principal receptor transducing TNF signals during lymphoid tissue development because TNFR2-deficient mice do not show changes in lymphatic organogenesis
[37]. Studies have also shown that TNFR1 mediates the immune response necessary to combat infection by microbes such as mycobacteria
[38] and Listeria monocytogenes
[39], while TNFR2 absence has a negligible effect on supporting this response
[40]. In addition, TNFR1 is the major receptor mediating host defense against viral infection
[41].