| Autor: |
de Juan, Alba, Tabtim-On, Darawan, Coillard, Alice, Becher, Burkhard, Goudot, Christel, Segura, Elodie |
| Předmět: |
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| Zdroj: |
Science Signaling; 10/15/2024, Vol. 17 Issue 858, p1-10, 10p |
| Abstrakt: |
Cytokines induce functional and metabolic adaptations in immune cells, typically through transcriptional responses that can be influenced by other extracellular signals and by intracellular factors. The binding of the cytokine interleukin-4 (IL-4) to its receptor induces the phosphorylation and activation of the transcription factor STAT6. The aryl hydrocarbon receptor (AhR), a transcription factor activated by various endogenous and microbe-derived metabolites, modulates the responses of immune cells to danger signals or inflammatory mediators such as cytokines. Here, we investigated cross-talk between the AhR and signaling stimulated by IL-4 in human and mouse monocytes. AhR activation was required for a subset of IL-4–induced transcriptional responses and inhibited the IL-4–induced metabolic switch to fatty acid β-oxidation. The promoters of the genes that were induced by IL-4 in an AhR-dependent manner lacked canonical AhR binding sites, implying a nongenomic mechanism of AhR action. Mechanistically, AhR activation reduced the activity of SHP-1, a phosphatase that targets and inhibits STAT6, and prolonged STAT6 phosphorylation and binding to specific target loci, thus extending the duration of STAT6 activity. Our results identify AhR as a key player in the molecular control of responses to IL-4 in monocytes and suggest a nongenomic mechanism through which AhR ligands may influence the functional responses of cells to IL-4. Editor's summary: The aryl hydrocarbon receptor (AhR), a transcription factor activated by various metabolites and xenobiotics, influences how immune cells respond to the cytokines that direct their differentiation and function. de Juan et al. found that activation of the AhR was required for the induction of a subset of transcripts by the cytokine interleukin-4 (IL-4) in human and mouse monocytes. AhR activation prolonged the IL-4–induced activation of the transcription factor STAT6 and increased the duration of STAT6 binding to the promoter of a gene encoding one of these transcripts. These findings identify a mechanism through which metabolites or other AhR ligands can influence the response of monocytes to cytokines. —Annalisa M. VanHook [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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