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Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis
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 pro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240914/ https://www.ncbi.nlm.nih.gov/pubmed/29172874 http://dx.doi.org/10.1177/1753425917742956 |
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author | Dai, Jun Kumbhare, Ajinkya Williams, Danielle A Youssef, Dima Yao, Zhi Q McCall, Charles E Gazzar, Mohamed El |
author_facet | Dai, Jun Kumbhare, Ajinkya Williams, Danielle A Youssef, Dima Yao, Zhi Q McCall, Charles E Gazzar, Mohamed El |
author_sort | Dai, Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6240914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-62409142019-01-01 Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis Dai, Jun Kumbhare, Ajinkya Williams, Danielle A Youssef, Dima Yao, Zhi Q McCall, Charles E Gazzar, Mohamed El Innate Immun Original Articles 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. SAGE Publications 2017-11-27 2018-01 /pmc/articles/PMC6240914/ /pubmed/29172874 http://dx.doi.org/10.1177/1753425917742956 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Dai, Jun Kumbhare, Ajinkya Williams, Danielle A Youssef, Dima Yao, Zhi Q McCall, Charles E Gazzar, Mohamed El Nfia deletion in myeloid cells blocks expansion of myeloid-derived suppressor cells during sepsis |
title | Nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
title_full | Nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
title_fullStr | Nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
title_full_unstemmed | Nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
title_short | Nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
title_sort | nfia deletion in myeloid cells blocks
expansion of myeloid-derived suppressor cells during sepsis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240914/ https://www.ncbi.nlm.nih.gov/pubmed/29172874 http://dx.doi.org/10.1177/1753425917742956 |
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