RelB suppresses type I Interferon signaling in dendritic cells
| Autor: | Himanshu Kumar, Hendrik J. Nel, Hemant Jaiswal, Jaring Schreuder, Bhupendra Singh Rawat, M. P. Kaushik, Prafullakumar Tailor, Shalin H. Naik, Irene Saha, Richa Mishra, Kuldeep Singh Chauhan, Ranjeny Thomas |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Immunology Newcastle disease virus Stimulation Dendritic cell differentiation Receptor Interferon alpha-beta Biology 03 medical and health sciences Mice 0302 clinical medicine NF-KappaB Inhibitor alpha Interferon medicine Animals Amino Acid Sequence Cells Cultured Crosses Genetic Cyclin-dependent kinase 1 RELB Transcription Factor RelB Cell Differentiation Dendritic cell Dendritic Cells Viral Load Cell biology IκBα 030104 developmental biology Gene Expression Regulation Interferon Type I NIH 3T3 Cells Signal transduction Peptides Spleen 030215 immunology medicine.drug Signal Transduction |
| Zdroj: | Cellular immunology. 349 |
| ISSN: | 1090-2163 |
| Popis: | 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 IκBα. 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. |
| Databáze: | OpenAIRE |
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