Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis

摘要

During an infection, the body increases the output of mature immune cells to fight off the udpathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) udcan sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. udHere we have combined mouse models with a single cell proteomics platform to show that in udresponse to toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells udproduce copious amount of diverse cytokines through the NF-κB signaling. Interestingly, the udcytokine production ability of HSPCs trumps mature immune cells in both magnitude and udbreadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of udmyeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid udmyeloid cell recovery during neutropenia. This study has uncovered a novel property of HSPCs udthat enables them to convert danger signals into versatile cytokine signals for regulation of stress udhematopoiesis.