IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription
| Autor: | Anand Balasubramani, Carlene L. Zindl, Ranjan Sen, Robin D. Hatton, Sarah K. Whitley, Casey T. Weaver, Gregory E. Crawford, Nathaniel M. Weathington, Yoichiro Shibata |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
STAT3 Transcription Factor Transcriptional Activation Immunology Regulatory Sequences Nucleic Acid Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) Animals Receptors Interleukin-1 Type II SOCS3 STAT3 Molecular Biology Transcription factor Psychological repression biology Interleukin-17 Transcription Factor RelA NF-κB Cell Biology DNA Cell biology Mice Inbred C57BL 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Phosphorylation Th17 Cells Transforming growth factor Signal Transduction |
| Popis: | Interleukin (IL)-1β plays a critical role in IL-6β– and transforming growth factor β (TGFβ)–initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remain poorly understood. We recently reported that IL-1β enhances STAT3 phosphorylation via NF-κB–mediated repression of SOCS3 to facilitate Il17 transcription and Th17 differentiation, identifying an effect of IL-1 signaling on proximal events of STAT3 signaling. Here, we show that IL-1β promotes STAT3 binding to key cis-elements that control IL-17 expression. Additionally, we demonstrate that the IL-1–induced NF-κB factor RelA directly regulates the Il17a/f loci in cooperation with STAT3. Our findings reveal that IL-1 impacts both proximal signaling events and downstream interactions between transcription factors and cis-regulatory elements to promote Il17a/f transcription and Th17 differentiation. |
| Databáze: | OpenAIRE |
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