Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Research Article
Long Non-Coding RNA Hotairm1 Promotes S100A9 Support of MDSC Expansion during Sepsis
Author(s): Tuqa Alkhateeb, Isatou Bah, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall and Mohamed El Gazzar*
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+CD11b+ cells.
Importantly, Hotairm1 knockdown in late sepsis Gr1.. View More»
DOI:
10.35248/2155-9899.20.11.600