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

Abstract

Background: Stem 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 TNFα are able to control the direction of the immune response. TNF-TNFR signaling plays a dual role: while the interaction of TNFα with TNFR1 mediates pro-inflammatory effects and cell death, its interaction with TNFR2 mediates antiinflammatory effects and cell survival. Main body: We 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 TNFα. 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 TNFα-TNFR2 dependent. Conclusions: NSCs are among the rare cells that express TNFR2 marker and are able to supress T cells. We believe TNFα-TNFR2 immune checkpoint signaling pathway could be responsible for this immunosuppressive effect.

Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury

“…administration, and they were more effective than free curcumin drugs. In addition, the level of malondialdehyde 49 and myeloperoxidase, 12 which are important to defend the neutralization of ROS production, increased significantly in ALI mice; however, Fe-Cur NP treatment decreased their levels, validating the ability of such nanozymes in removing ROS in mice bodies ( Figure 6 e,f).…”

Role of the Interaction of Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors 1 and 2 in Bone-Related Cells

“…The expression of TNFR2 is restricted compared to the ubiquitous expression of TNFR1. TNFR2 is expressed on endothelial cells, mesenchymal stem cells, and immune cells, such as macrophages, monocytes, T cells, B cells, and NK cells [42][43][44][45][46][47], and neural cells [48]. The extracellular region of TNFR2 contains CRDs (CRD1, CRD2, CRD3, and CRD4) as observed in TNFR1 [31,32], and TNFR2 exists in its trimetric form before stimulation by TNF-α.…”

The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response

“…Myeloid-derived suppressor cells (MDSCs), an inflammation-induced population, appears to be the one myeloid population that specifically requires TNFR2 for its induction and suppressive functions ( Zhao et al, 2012 ; Hu et al, 2014 ; Polz et al, 2014 ; Ham et al, 2015 ). Finally, the TNF-α/TNFR2 signaling pathway has very recently been shown to be a key regulatory factor for the immunosuppressive effect of mesenchymal stem cells and neural and endothelial progenitor cells ( Beldi et al, 2020 ; Naserian et al, 2020 ; Shamdani et al, 2020 ). Overall, these observations support the existence of a TNFR2-dependant network of immunosuppressive cells that have been ignored until recently, that could help broadening the therapeutic landscape.…”