TNFα-TNFR2 signaling pathway in control of the neural stem/progenitor cell immunosuppressive effect: Different experimental approaches to assess this hypothetical mechanism behind their immunological function

BackgroundStem cells have a vast range of functions from tissue regeneration to immunoregulation. They have the ability to modulate immune responses and change the progression of different inflammatory and autoimmune disorders. Tumor cells share many characteristics of stem/progenitor cells too. Both can inhibit effector T cells and other immune cells, while inducing regulatory T cells (T regs), thus, reducing the production of pro-inflammatory cytokines and increasing the production of anti-inflammatory ones. In this context, some cytokines like TNF alpha are able to control the direction of the immune response. TNF-TNFR signaling plays a dual role: while the interaction of TNF alpha with TNFR1 mediates pro-inflammatory effects and cell death, its interaction with TNFR2 mediates anti-inflammatory effects and cell survival.Main bodyWe think the expression of TNFR2 confers a level of immunomodulatory properties to its expressing cell and this could be crucially important, particularly, for stem/progenitor and tumor cells. This idea has been already proven in many TNFR2(+) cells. Different immunosuppressive cells like T regs, regulatory B cells (B regs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) express TNFR2 and are able to suppress immune cells in presence of TNF alpha. The other category of rare cells that express TNFR2 is neural cells (NCs). Although little is known about the immunological function of these latter cells, few studies showed their progenitors are able to suppress T cells. Therefore, we hypothesize that the immunosuppressive effect of neural stem cells (NSCs) is potentially TNF alpha -TNFR2 dependent.ConclusionsNSCs are among the rare cells that express TNFR2 marker and are able to supress T cells. We believe TNF alpha -TNFR2 immune checkpoint signaling pathway could be responsible for this immunosuppressive effect.