Shanghai team: PRMT6 represses IL-1β and limits colitis in mice; p50 inhibition restores PRMT6
Researchers found PRMT6 reduced in human IBD datasets. In mice, its loss worsened colitis, while p50 inhibition restored PRMT6 and protected the animals.
A team from the National Key Laboratory of Immunity and Inflammation at Naval Medical University in Shanghai, together with colleagues from several Chinese hospitals, reported in Nature Communications that the enzyme PRMT6 restrains intestinal inflammation in mouse models of colitis doi.org
Nature Communicationsdoi.orgOpen source ↗. The authors screened epigenetic molecules in published human datasets of inflammatory bowel disease (IBD) and found PRMT6 consistently downregulated in IBD samples compared with healthy controls
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Nature Communicationsdoi.orgOpen source ↗.
IBD is a chronic inflammatory disorder driven by dysregulated immune responses, and macrophage-mediated inflammation is central to its pathology. In colon biopsy samples, suppression of Prmt6 and induction of Il1b co-occurred in the myeloid compartment. The authors take this as an indication that PRMT6 limits macrophage-driven inflammation doi.org
Nature Communicationsdoi.orgOpen source ↗.
Prmt6 deficiency in mice
Mice lacking Prmt6 were more susceptible to colitis induced by either DSS or TNBS. The disease was characterized by exacerbated tissue damage and a systemic elevation of IL-1β doi.org
Nature Communicationsdoi.orgOpen source ↗. Transcriptomic profiling showed that PRMT6 deficiency selectively upregulated Il1b among inflammatory mediators
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Nature Communicationsdoi.orgOpen source ↗.
Epigenetic mechanism and the role of p50
According to the authors, PRMT6 suppresses Il1b transcription by interacting with RBBP5 and disrupting assembly of the SET1A complex. This reduces H3K4me3 enrichment at the Il1b promoter. The effect does not depend on the canonical H3R2me2a catalytic activity of PRMT6 doi.org
Nature Communicationsdoi.orgOpen source ↗.
During inflammation, PRMT6 itself is transcriptionally silenced by p50, a subunit of NF-κB. Pharmacological inhibition of p50 restored PRMT6 expression and protected mice from DSS-induced colitis in a PRMT6-dependent manner doi.org
Nature Communicationsdoi.orgOpen source ↗.
The authors describe the findings as proof of principle for targeting the p50–PRMT6–IL-1β axis in IBD doi.org
Nature Communicationsdoi.orgOpen source ↗. The functional experiments were carried out in mouse models, and the human data come from published datasets and colon biopsy samples.
