IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.
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.
Duke Scholars
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Related Subject Headings
- Transcriptional Activation
- Transcription Factor RelA
- Th17 Cells
- Signal Transduction
- STAT3 Transcription Factor
- Regulatory Sequences, Nucleic Acid
- Receptors, Interleukin-1 Type II
- Mice, Inbred C57BL
- Interleukin-17
- DNA
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcriptional Activation
- Transcription Factor RelA
- Th17 Cells
- Signal Transduction
- STAT3 Transcription Factor
- Regulatory Sequences, Nucleic Acid
- Receptors, Interleukin-1 Type II
- Mice, Inbred C57BL
- Interleukin-17
- DNA