IRF8: Mechanism of Action and Health Implications
Interferon regulatory factor 8 (IRF8) is a transcription factor of the IRF protein family. IRF8 was originally identified as an essentialfactor for myeloid cell lineage commitment and differentiation. Deletion of <i>Irf8</i> leads to massive accumulation of CD11b<sup>+</sup>G...
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MDPI AG
2022-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/17/2630 |
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| author | Hannah R. Moorman Yazmin Reategui Dakota B. Poschel Kebin Liu |
| author_facet | Hannah R. Moorman Yazmin Reategui Dakota B. Poschel Kebin Liu |
| author_sort | Hannah R. Moorman |
| collection | DOAJ |
| description | Interferon regulatory factor 8 (IRF8) is a transcription factor of the IRF protein family. IRF8 was originally identified as an essentialfactor for myeloid cell lineage commitment and differentiation. Deletion of <i>Irf8</i> leads to massive accumulation of CD11b<sup>+</sup>Gr1<sup>+</sup> immature myeloid cells (IMCs), particularly the CD11b<sup>+</sup>Ly6C<sup>hi/+</sup>Ly6G<sup>−</sup> polymorphonuclear myeloid-derived suppressor cell-like cells (PMN-MDSCs). Under pathological conditions such as cancer, <i>Irf8</i> is silenced by its promoter DNA hypermethylation, resulting in accumulation of PMN-MDSCs and CD11b<sup>+</sup> Ly6G<sup>+</sup>Ly6C<sup>lo</sup> monocytic MDSCs (M-MDSCs) in mice. IRF8 is often silenced in MDSCs in human cancer patients. MDSCs are heterogeneous populations of immune suppressive cells that suppress T and NK cell activity to promote tumor immune evasion and produce growth factors to exert direct tumor-promoting activity. Emerging experimental data reveals that IRF8 is also expressed in non-hematopoietic cells. Epithelial cell-expressed IRF8 regulates apoptosis and represses Osteopontin (OPN). Human tumor cells may use the IRF8 promoter DNA methylation as a mechanism to repress IRF8 expression to advance cancer through acquiring apoptosis resistance and OPN up-regulation. Elevated OPN engages CD44 to suppress T cell activation and promote tumor cell stemness to advance cancer. IRF8 thus is a transcription factor that regulates both the immune and non-immune components in human health and diseases. |
| first_indexed | 2024-03-10T01:58:08Z |
| format | Article |
| id | doaj.art-b1dd1f8f30b74575b3e72a6913ce9707 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:58:08Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b1dd1f8f30b74575b3e72a6913ce97072023-11-23T12:54:15ZengMDPI AGCells2073-44092022-08-011117263010.3390/cells11172630IRF8: Mechanism of Action and Health ImplicationsHannah R. Moorman0Yazmin Reategui1Dakota B. Poschel2Kebin Liu3Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USADepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USAInterferon regulatory factor 8 (IRF8) is a transcription factor of the IRF protein family. IRF8 was originally identified as an essentialfactor for myeloid cell lineage commitment and differentiation. Deletion of <i>Irf8</i> leads to massive accumulation of CD11b<sup>+</sup>Gr1<sup>+</sup> immature myeloid cells (IMCs), particularly the CD11b<sup>+</sup>Ly6C<sup>hi/+</sup>Ly6G<sup>−</sup> polymorphonuclear myeloid-derived suppressor cell-like cells (PMN-MDSCs). Under pathological conditions such as cancer, <i>Irf8</i> is silenced by its promoter DNA hypermethylation, resulting in accumulation of PMN-MDSCs and CD11b<sup>+</sup> Ly6G<sup>+</sup>Ly6C<sup>lo</sup> monocytic MDSCs (M-MDSCs) in mice. IRF8 is often silenced in MDSCs in human cancer patients. MDSCs are heterogeneous populations of immune suppressive cells that suppress T and NK cell activity to promote tumor immune evasion and produce growth factors to exert direct tumor-promoting activity. Emerging experimental data reveals that IRF8 is also expressed in non-hematopoietic cells. Epithelial cell-expressed IRF8 regulates apoptosis and represses Osteopontin (OPN). Human tumor cells may use the IRF8 promoter DNA methylation as a mechanism to repress IRF8 expression to advance cancer through acquiring apoptosis resistance and OPN up-regulation. Elevated OPN engages CD44 to suppress T cell activation and promote tumor cell stemness to advance cancer. IRF8 thus is a transcription factor that regulates both the immune and non-immune components in human health and diseases.https://www.mdpi.com/2073-4409/11/17/2630IRF8myeloid cellsOPNMDSCsimmunotherapy |
| spellingShingle | Hannah R. Moorman Yazmin Reategui Dakota B. Poschel Kebin Liu IRF8: Mechanism of Action and Health Implications Cells IRF8 myeloid cells OPN MDSCs immunotherapy |
| title | IRF8: Mechanism of Action and Health Implications |
| title_full | IRF8: Mechanism of Action and Health Implications |
| title_fullStr | IRF8: Mechanism of Action and Health Implications |
| title_full_unstemmed | IRF8: Mechanism of Action and Health Implications |
| title_short | IRF8: Mechanism of Action and Health Implications |
| title_sort | irf8 mechanism of action and health implications |
| topic | IRF8 myeloid cells OPN MDSCs immunotherapy |
| url | https://www.mdpi.com/2073-4409/11/17/2630 |
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