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Abstract
<p class="first" id="P1">The myeloid-related protein S100A9 reprograms Gr1
<sup>+</sup>CD11b
<sup>+</sup> 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
<sup>+</sup>CD11b
<sup>+</sup> precursors 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
<sup>+</sup>CD11b
<sup>+</sup> 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.
</p>