Decoding TNF receptor superfamily control of CD4+Foxp3+ Regulatory T cell-mediated tolerance: implications for the treatment of graft‑versus‑host disease - PubMed
5 hours ago
- #Tregs
- #TNFRSF
- #GvHD
- Allogeneic transplantation's efficacy is often limited by graft-versus-host disease (GvHD), highlighting the need for precision tolerance strategies.
- CD4+Foxp3+ regulatory T cells (Tregs) are promising for targeted therapy, though challenges remain in expanding functional Tregs ex vivo and in vivo.
- TNF Receptor Superfamily (TNFRSF) members, including TNFR2, OX40, CD40, Fas, CD27, 4-1BB, GITR, and DR3, play critical and dichotomous roles in Treg function.
- Agonism of TNFR2 or DR3 can selectively expand Tregs while preserving graft-versus-leukemia (GvL) effects.
- CD27 and 4-1BB are useful markers for isolating highly suppressive Treg subsets, enhancing targeted therapies.
- Translational challenges include the context-dependent effects of OX40 and GITR on Tregs and the vulnerability of Tregs to Fas-mediated apoptosis during ex vivo expansion.
- CD40-CD40L blockade can complement Treg therapies by empowering endogenous Tregs, offering a synergistic approach.
- The review provides a roadmap for leveraging selective agonism, blockade, or phenotypic selection to optimize Treg-based therapies for GvHD.