1. Figure 3 TNFSF activities enhancing immune cell activation
Figure 3 | TNFSF activities enhancing immune cell activation. The simplified diagram highlights the possible interactions between TNF superfamily (TNFSF) ligands and TNF receptor superfamily (TNFRSF) proteins expressed on several cells in the immune system (antigen-presenting cells (APCs), B cells, and T cells). Driven by the appropriate antigen, T cells can receive TNFRSF signals through OX40, glucocorticoid-induced TNF receptor-related protein (GITR), death receptor 3 (DR3), CD27, and 4-1BB. These signals enhance their activation, promote division and survival to augment the size of the autoreactive pool, induce differentiation of follicular helper T (TFH) cells that control antibody responses and induce the expression of cytokines that drive tissue pathology. APCs (dendritic cells and macrophages), via CD40, can upregulate MHC molecules, co-stimulatory ligands (including TNFSF molecules) and inflammatory cytokines, which aid the T-cell response. B cells can receive signals from CD40, CD27, GITR, B-cell-activating factor (BAFF) receptor (BAFFR), B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI). These signals drive activation, division and survival, class switching, and plasma cell differentiation, resulting in production of pathogenic autoantibodies. Reverse signalling through membrane-expressed TNFSF ligands such as OX40 ligand (OX40L), CD70 and 4-1BBL, expressed on dendritic cells, macrophages and B cells, can also augment production of inflammatory cytokines and help B cell differentiation. Other reported activities of TNFRSF signalling on immune cells such as mast cells, eosinophils, neutrophils, basophils, Natural killer T cells and innate lymphoid cells are not shown, but these can further result in production of inflammatory mediators that contribute to tissue pathology and amplify the T-cell and B-cell response.
Croft, M. & Siegel, R. M. (2017) Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases
Nat. Rev. Rheumatol. doi: /nrrheum