| First Author | Ahad A | Year | 2019 |
| Journal | iScience | Volume | 19 |
| Pages | 996-1011 | PubMed ID | 31522122 |
| Mgi Jnum | J:342866 | Mgi Id | MGI:6717573 |
| Doi | 10.1016/j.isci.2019.08.024 | Citation | Ahad A, et al. (2019) NCoR1: Putting the Brakes on the Dendritic Cell Immune Tolerance. iScience 19:996-1011 |
| abstractText | Understanding the mechanisms fine-tuning immunogenic versus tolerogenic balance in dendritic cells (DCs) is of high importance for therapeutic approaches. We found that NCoR1-mediated direct repression of the tolerogenic program in conventional DCs is essential for induction of an optimal immunogenic response. NCoR1 depletion upregulated a wide variety of tolerogenic genes in activated DCs, which consequently resulted in increased frequency of FoxP3(+) regulatory T cells. Mechanistically, NCoR1 masks the PU.1-bound super-enhancers on major tolerogenic genes after DC activation that are subsequently bound by nuclear factor-kappaB. NCoR1 knockdown (KD) reduced RelA nuclear translocation and activity, whereas RelB was unaffected, providing activated DCs a tolerogenic advantage. Moreover, NCoR1(DC-/-) mice depicted enhanced Tregs in draining lymph nodes with increased disease burden upon bacterial and parasitic infections. Besides, adoptive transfer of activated NCoR1 KD DCs in infected animals showed a similar phenotype. Collectively, our results demonstrated NCoR1 as a promising target to control DC-mediated immune tolerance. |
