Project description:To investigate the function of Neuropilin-1 (NRP-1) in Foxp3+ regulatory T (Treg) cell stability and function, we cultured naïve CD4+ T cells under induced Treg cell (iTreg)-differentiating condition. We then flow sorted NRP-1+ and NRP-1- iTreg cells and performed gene expression profiling analysis.
Project description:Allogeneic hematopoietic stem cell transplantation (SCT) is a curative treatment for hematological cancers but outcomes are limited by graft-versus-host disease (GVHD). IL-6R expression and IL-6 signaling are most pronounced in CD4 T cells and monocytesand promote acute GVHD (aGVHD) in preclinical models by inducing Th17 and Th22 differentiation. To understand the effect of IL-6 signaling on T cell responses in humans, we performed CITE-seq on circulating CD14+ monocytes and CD4+ T cells from HSCT recipients in a randomized controlled clinical trial receiving tocilizumab (TCZ) or placebo who did not develop acute GVHD. A third placebo treated group were analyzed prior to their development of aGVHD. IL-6 inhibition promoted Type I IFN-associated transcriptional programs in both CD4+ T cells and CD14+ monocytes relative to those from placebo-treated recipients