Epigenetic eraser histone deacetylase 1 (HDAC1) limits AIEC-induced inflammatory response in intestinal epithelial cells

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Denizot, Jérémy | Chervy, Mélissa | Dambrine, Flavie | Le Bourhis, Lionel | Allez, Matthieu | Barnich, Nicolas

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International audience. Histone deacetylase HDAC1 is necessary to prevent AIEC bacteria entry within intestinal epithelial cells (IECs) (Chervy et al., 2022). To further study the role of HDAC1 in the crosstalk between AIEC and IECs, we performed a transcriptomic analysis of Caco-2 cells silenced for HDAC1 gene and infected by AIEC LF82 bacteria. Gene set enrichment analysis (GSEA) revealed that HDAC1 silencing leads to uncontrolled inflammatory genes expression upon AIEC infection. Indeed, CXCL8, TNF, IL1b, IL1a genes expression is induced by AIEC infection but is even more induced in the absence of HDAC1. Using transcriptomic analysis of ileal samples from CD patients, we found an inverse correlation between the expression level of these genes and HDAC1 expression, reinforcing the link between HDAC1 and inflammatory genes expression (in CD patients). IECs transcriptomic analysis also revealed that HDAC1 limits AIEC-induced AP-1 transcription factor (JunB/JunD) expression. In patients, we observed that JUN-D expression level is negatively correlated to HDAC1 expression and that JunD is more expressed in AIEC-colonized CD patients compared to non-colonized patients. Altogether, these data show that HDAC1 is central in the control of the inflammatory response of IECs to AIEC infection and that JunD transcription factor might be the missing link between AIEC infection and inflammatory response by recruiting HDAC1 to inflammatory gene promoters to modify chromatin structure and prevent uncontrolled inflammation.

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