Treg-specific IL-6R signaling: a novel role in the regulation of the intestinal epithelium

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Treg IL-6R knockout mice displayed increased susceptibility to DSS colitis, highlighting the need for IL-6R signaling in epithelial protection.
In vitro assessments indicated that Tregs released soluble IL-6R, facilitating IL-6 trans-signaling to epithelial cells.
RNA-seq showed transcriptional downregulation in intestinal epithelial cells of Treg IL-6R knockout mice, affecting survival and repair pathways.
IL-6 trans-signaling in human organoids resulted in enhanced STAT3 activation compared to IL-6 alone, indicating its critical role.

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Analysis shows Tregs regulate intestinal epithelial integrity in colitis models, suggesting new therapeutic targets for IBD.

Klatt et al. (2025) studied this question.

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