Long Non-Coding RNA Hotairm1 Promotes S100A9 Support of MDSC Expansion during Sepsis.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) expand during mouse and human sepsis, but the mechanism responsible for this is unclear. We previously reported that nuclear transport of S100A9 protein programs Gr1⁺CD11b⁺ myeloid precursors into MDSCs in septic mice. Here, we show that long non-coding RNA Hotairm1 converts MDSCs from an activator to a repressor state. Mechanistically, increased Hotairm1 expression in MDSCs in mice converted S100A9 from a secreted proinflammatory mediator to an immune repressor by binding to and shuttling it from cytosol to nucleus during late sepsis. High Hotairm1 levels were detected in exosomes shed from MDSCs from late septic mice. These exosomes inhibited lipopolysaccharide-stimulated secretion of S100A9 from early sepsis Gr1⁺C

SUBMITTER: Alkhateeb T 

PROVIDER: S-EPMC7744002 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature