Title
IL-10 Induces an Immune Repressor Pathway in Sepsis by Promoting S100A9 Nuclear Localization and MDSCdsc Development
Document Type
Article
Publication Date
10-1-2018
Description
The myeloid-related protein S100A9 reprograms Gr1+CD11b+ myeloid precursors into myeloid-derived suppressor cells (MDSCs) during murine sepsis. Here, we show that the immunosuppressive cytokine IL-10 supports S100A9 expression and its nuclear localization in MDSCs to function as immune repressors. To support this new concept, we showed that antibody mediated IL-10 blockade in wild-type mice after sepsis induction inhibited MDSC expansion during late sepsis, and that ectopic expression of S100A9 in Gr1+CD11b+ cells from S100A9 knockout mice switched them into the MDSC phenotype only in the presence of IL-10. Knockdown of S100A9 in MDSCs from wild-type mice with late sepsis confirmed our findings in the S100A9 knockout mice. We also found that while both IL-6 and IL-10 can activate S100A9 expression in naive Gr1+CD11b+ cells, only IL-10 can induce S100A9 nuclear localization. These results support that IL-10 drives the molecular path that generates MDSCs and enhances immunosuppression during late sepsis, and inform that targeting this immune repressor path may improve sepsis survival in mice.
Citation Information
Bah, Isatou; Kumbhare, Ajinkya; Nguyen, Lam; McCall, Charles E.; and El Gazzar, Mohamed. 2018. IL-10 Induces an Immune Repressor Pathway in Sepsis by Promoting S100A9 Nuclear Localization and MDSCdsc Development. Cellular Immunology. Vol.332 32-38. https://doi.org/10.1016/j.cellimm.2018.07.003 PMID: 30025864 ISSN: 0008-8749