The pro-Inflammatory cytokines effects on mobilization, self-renewal and differentiation of hematopoietic stem cells

Abstract Different mature immune cells are being produced during infection by hematopoietic stem cells in order to compensate the required cells battling against pathogens. A wide variety of pro-inflammatory cytokines like G-CSF, TNFα, IFNα, IL-1, IL-6, etc. affect HSCs and provoke different responses including maintenance, survival, activation, proliferation, differentiation, and immune responses. The exact mechanisms of translating pathogen sensing into cytokine signals for regulating HSCs are not fully understood yet. Moreover, the interaction between these cytokines modulating different responses have to be well established in order to understand HSC responses during inflammatory complications, since several different effects have been attributed to cytokines in various conditions. IFNγ demonstrates pleiotropic influences on various cell types such as HSCs and HSPCs. It can induce HSC proliferation, quiescence, reconstitution, mobilization and differentiation. Similar to other inflammatory cytokines including IL-6, IL-3, IL-2, and GM-CSF, G-CSF is a significant mobilizing factor. It contributes to increase phenotypic HSCs in bone marrow (BM), induction of HSC cycling and quiescence, and declined long-term repopulating activity of HSCs. Growth inhibition and apoptosis induction have been understood to be elicited by TNFα, similar to IFNγ. IL-1 is a significant component for inflammatory responses, which can synergize with TNFα enhancing neutrophil production in bone marrow. It has been demonstrated that HSPC-derived cytokines, especially IL-6, is important in the functional context for promoting myelopoiesis in vitro and in vivo. Therefore, understanding their effects on HSCs in normal and stressed situation can be helpful in managing different inflammatory complications.