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Publication : RelB suppresses type I Interferon signaling in dendritic cells.

First Author  Saha I Year  2020
Journal  Cell Immunol Volume  349
Pages  104043 PubMed ID  32044112
Mgi Jnum  J:294539 Mgi Id  MGI:6453354
Doi  10.1016/j.cellimm.2020.104043 Citation  Saha I, et al. (2020) RelB suppresses type I Interferon signaling in dendritic cells. Cell Immunol 349:104043
abstractText  Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs led to RelB induction coinciding with fall in IFN signatures; conforming with the observation Relb expression reduced TLR stimulated IFN induction along with decrease in ISGs. Towards understanding mechanism, we show that effects of RelB are mediated by increased levels of IkappaBalpha. We demonstrate that RelB dampened antiviral responses by lowering ISG levels and the defect in cDC2 development in RelB null mice can be rescued in Ifnar1(-/-) background. Overall, we propose a novel role of RelB as a negative regulator of the type I IFN signaling pathway; fine tuning development of cDC2 subtype.
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