Document Type
Article
Publication Date
11-17-2017
Description
Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis. We used a chronic model of sepsis in mice to show that S100A9 release from MDSCs and circulating phagocytes decreases after early sepsis and that targeting the S100a9 gene improves survival. Surprisingly, we find that intracellular S100A9 protein translocates from the cytosol to nucleus in Gr1+CD11b+ MDSCs during late sepsis and promotes expression of miR-21 and miR-181b immune repressor mediators. We further provide support of this immunosuppression pathway in human sepsis. This study may inform a new therapeutic target for improving sepsis outcome.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Citation Information
Dai, Jun; Kumbhare, Ajinkya; Youssef, Dima; McCall, Charles E.; and El Gazzar, Mohamed. 2017. Intracellular S100A9 Promotes Myeloid-Derived Suppressor Cells During Late Sepsis. Frontiers in Immunology. Vol.8(NOV). https://doi.org/10.3389/fimmu.2017.01565
Copyright Statement
© 2017 Dai, Kumbhare, Youssef, McCall and El Gazzar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.