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Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis #MMPMID29172874
Dai J; Kumbhare A; Williams DA; Youssef D; Yao ZQ; McCall CE; El Gazzar M
Innate Immun 2018[Jan]; 24 (1): 54-65 PMID29172874show ga
Sepsis-induced immunosuppression increases the risk of chronic infection and reduces survival. Myeloid-derived suppressor cells (MDSCs) expand in the bone marrow and spleen during murine polymicrobial sepsis, contributing to immunosuppression. A better understanding of molecular controls of MDSC production is needed to identify treatment targets. We previously reported that miR-21 and miR-181b couple with transcription factor NFI-A to induce MDSCs during murine sepsis. Here, we expand upon these observations by showing that conditional deletion of the Nfia gene in the myeloid lineage precludes MDSC development. NFI-A-deficient Gr1(+)CD11b(+) myeloid cells are not immunosuppressive and differentiate normally into macrophages and dendritic cells. In contrast, ectopically expressed NFI-A prevents differentiation of these immature Gr1(+)CD11b(+) cells, while converting them into MDSCs. In addition, NFI-A-deficient Gr1(+)CD11b(+) cells decreased, and cells transfected with NFI-A increase expression of miR-21 and miR181b. Our results support a myeloid cell loop in which NFI-A and miR-21 and miR-181b sustain Gr1(+)CD11b(+) MDSC-dependent immunosuppression during sepsis.
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Innate+Immun 2018 ; 24 (1): 54-65
