Discorea nipponica saponins restore the Th17/Treg balance in aplastic anemia through the Notch/RBPJκ/FOXP3/RORγt axis

Abstract

T cell differentiation is a key pathological process of aplastic anemia (AA). Tregs and Th17 must be balanced for efficient immune tolerance. Discorea nipponica saponins (DNS) improves the recovery from hematopoiesis in AA models through its ability to increase the number of T-helper cells whilst decreasing the percentage of T-cytotoxic cells in AA mice. However, the mechanisms by which DNS leads to these therapeutic effects remains largely undefined. Here, we explored the mechanism(s) by which DNS regulates T cell subsets in mouse AA models. BALB/c male mice were used to establish the AA model using 137Cs irradiation and intraperitoneal injection with cyclophosphamides and Chloramphenicol. Mice were administrated DNS/Tripterygium wilfordii polyglycoside tablets (TW)/cyclosporine A (CsA)/distilled water via gavage each day for 14 days. Peripheral blood, spleen and bone marrow were obtained. Bone marrow morphology, Notch/RBPJκ/FOXP3/RORγt signaling and molecules regulating Th17/Treg balance were evaluated. We found that DNS-M attenuated pancytopenia in mouse AA models. DNS-M could not only suppressed Th 17 cell numbers and RORγt expression, but enhanced the prevalence of Treg cells and Foxp3 expression. Moreover, DNS-M modulated the level of Notch1, Jagged1, RBPJκ, FOXP3, RORγt, DLL4 in AA models. These data suggest that the administration of DNS-M exhibits therapeutic effects through restoring the Th17/Treg cell balance in AA mice through its regulation of the Notch/RBPJκ/FOXP3/RORγt pathway. Keywords: Discorea nipponica saponins, Aplastic anemia, T cell differentiation, Notch pathway