| First Author | Dai J | Year | 2018 |
| Journal | Innate Immun | Volume | 24 |
| Issue | 1 | Pages | 54-65 |
| PubMed ID | 29172874 | Mgi Jnum | J:272039 |
| Mgi Id | MGI:6282728 | Doi | 10.1177/1753425917742956 |
| Citation | Dai J, et al. (2018) Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis. Innate Immun 24(1):54-65 |
| abstractText | 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. |
