Feb. 20(MON) 16:30 / Auditorium (1F), PBC Commensal-induced inflammatory cytokines control the steady state expansion of multipotent progenitors Feb. 20(MON) 16:30 / Auditorium (1F), PBC Seungwon Lee POSTECH Hematopoietic stem and progenitor cells (HSPCs) produce all the blood cells in response to hematopoietic stress, but the regulation of HSPCS in the absence of infection remains unclear. Here we reveal that gut microbiota controls the homeostasis of HSPCs by increasing numbers of multipotent progenitors (MPPs). Antibiotic-treated or germ-free (GF) mice elicits decreases of MPPs, but not HSCs, by attenuating cell cycle progression. Mechanistically, gut microbiota indirectly regulates expansion of MPPs in a cell-extrinsic manner through TLRs in hematopoietic lineage cells, which maintains a tonic production of inflammatory cytokines in steady state, such as TNFα, IL-1β, and IL-6. Finally, the mononuclear phagocyte system (MPS), in particular dendritic cells (DCs) that are clustered at the perivascular BM niche, is responsible for producing inflammatory cytokines in a commensal-dependent way. Our findings uncover an as-yet-unknown role of gut microbiota in expansion of MPPs at the BM microenvironment, acting as a cue for maintaining the homeostatic balance of HSPCs. Inquiry: Dr. You Jeong Lee (279-2359) or AIM Administrative Team (Tel.279-0641, E-mail: hisgrace99@ibs.re.kr)