microRNAs as potential regulators of myeloid-derived suppressor cell expansion

Abstract

Proper development and activation of cells of the myeloid lineage are critical for supporting innate immunity. This myelopoiesis is orchestrated by interdependent interactions between cytokine receptors, transcription factors and, as recently described, microRNAs (miRNAs). miRNAs contribute to normal and dysregulated myelopoiesis. Alterations in myelopoiesis underlie myeloid-derived suppressor cell (MDSC) expansion, a poorly understood heterogeneous population of immature and suppressive myeloid cells that expand in nearly all diseases where inflammation exists. MDSCs associated with inflammation often have immunosuppressive properties, but molecular mechanisms responsible for MDSC expansion are unclear. Emerging data implicate miRNAs in MDSC expansion. This review focuses on miRNAs that contribute to myeloid lineage differentiation and maturation under physiological conditions, and introduces the concept that altered miRNA expression my underlie expansion and accumulation of MDSCs. We divide our miRNAs into those with potential to promote MDSC expansion and two with known direct links to MDSC expansion, miR-223 and miR-494.

Keywords: Myelopoiesis; innate immunity; microRNAs; myeloid-derived suppressor cells.

Figure 1.

A schematic of myeloid lineage development and differentiation depicting how changes in the expression of some miRNAs can disrupt myeloid progenitor differentiation and generate MDSCs. MDSCs may arise before or after the GMP stage, as they exist at different myeloid progenitor and precursor stages. Not all miRNAs suspected to regulate MDSC biology are shown; only those that have been investigated directly in MDSCs are shown. The lymphoid and erythroid differentiation paths are not discussed in this review and thus are not shown. HSC: hematopoietic stem cell; MPP: multipotent progenitor; LMPP: lymphoid-primed multipotent progenitor; CMP: common myeloid progenitor; GMP: granulocyte-macrophage progenitor.