Improving adoptive treg cell therapy by blocking treg cell-mediated pathogenic Th17 cell generation (PRJCA029869)

CD4+Foxp3+ regulatory T (Treg) cells play a crucial role in maintaining tolerance to self-antigens and preventing excessive immune activation. However, the process of translating adoptive Treg cell therapy into clinical practice still presents significant challenges. We identified that adoptive Treg cell therapy unexpectedly leads to the increased differentiation of IL-6 and TGF-ß-dependent pathogenic Th17 cells. We elucidated that Treg cells promote Th17 cell differentiation by suppressing IL-2 secretion of effector T (Teff) cells and competitively consuming IL-2.In addition, inhibition of IL-2 signaling not only promotes Th17 cell-associated transcriptional programs but also enhances the pro-inflammatory properties of Th17 cells. Based on this, we propose a combined therapeutic strategy combining adoptive transfer of Treg cells with blockade of the IL-6/STAT3 signaling pathway