Generation of mature activated regulatory myeloid cells: Differential effects of retinoic acid on myelopoiesis versus dendropoiesis (P1064)

Abstract

Abstract Myeloid cells are increasingly recognized for their potent regulatory abilities. However, factors influencing regulatory myeloid cell (regMC) differentiation remain poorly understood. Retinoic acid (RA) is a steroid hormone important in regulating mucosal (gut) immunity. RA also promotes myeloid differentiation. We hypothesize that RA during differentiation will promote regMC formation (both regulatory DCs and macrophages). Using in vitro differentiation of myeloid cells with GM-CSF with or without RA, we found that day 6-7 RA BM-MCs were more mature/activated (i.e. increased expression of CD80, CD86, and MHCII) than control BM-MCs. Importantly, RA BM-MCs also had increased expression of the inhibitory marker PD-L1. Functionally, these RA BM-MCs expressed increased intracellular IL-10 and induced an increased percentage of T regulatory cells in vitro compared to controls. Notably, RA BM-MCs suppressed the proliferation of responder immune cells even after inflammatory (LPS) challenge. Surprisingly, CD11c+ (DCs) within the RA BM-MC population were not the suppressive population. Rather, the suppressive cells were CD11c-CD11b+Ly6Cint/low and likely represent a regulatory monocyte or other myeloid precursor population. Additional studies characterizing these cells are ongoing. These results suggest that RA has differential effects on myelopoiesis versus dendropoeisis which produce non-DC regMCs.