Unknown

Dataset Information

0

MiR-106a deficiency attenuates inflammation in murine IBD models.


ABSTRACT: Pro-inflammatory cytokine TNF? antagonizes regulatory T cell (Treg) suppressive function with a measurable reduction of IL-10 protein secretion. Tregs are critical to suppress excessive immune activation, particularly within the intestine where high antigenic loads elicit chronic subclinical immune activation. Employing a TNF?-driven murine inflammatory bowel disease (IBD) model (TNF?ARE/+), which mirrors the Treg expansion and transmural ileitis seen in Crohn's disease, we demonstrate that the TNF?-mediated loss of Treg suppressive function coincides with induction of a specific miRNA, miR-106a in both humans and mice, via NF?B promoter binding to suppress post-transcriptional regulation of IL-10 release. Elevation of miR-106a and impaired Treg function in this model recapitulate clinical data from IBD patients. MiR-106a deficiency promotes Treg induction, suppressive function and IL-10 production in vitro. MiR-106a knockout attenuated chronic murine ileitis, whereas T cell restricted deficiency of miR-106a attenuated adoptive transfer colitis. In both models, attenuated inflammation coincided with suppression of both Th1 and Th17 cell subset expansion within the intestinal lamina propria. Collectively, our data demonstrate impaired Treg suppressive function in a murine IBD model consistent with human disease and support the potential for inhibition of miR-106a as a future therapeutic approach to treat chronic inflammatory conditions including IBD.

SUBMITTER: Sanctuary MR 

PROVIDER: S-EPMC6301105 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

miR-106a deficiency attenuates inflammation in murine IBD models.

Sanctuary Megan R MR   Huang Rick H RH   Jones Ashleigh A AA   Luck Marisa E ME   Aherne Carol M CM   Jedlicka Paul P   de Zoeten Edwin F EF   Collins Colm B CB  

Mucosal immunology 20181016 1


Pro-inflammatory cytokine TNFα antagonizes regulatory T cell (Treg) suppressive function with a measurable reduction of IL-10 protein secretion. Tregs are critical to suppress excessive immune activation, particularly within the intestine where high antigenic loads elicit chronic subclinical immune activation. Employing a TNFα-driven murine inflammatory bowel disease (IBD) model (TNF<sup>ΔARE/+</sup>), which mirrors the Treg expansion and transmural ileitis seen in Crohn's disease, we demonstrat  ...[more]

Similar Datasets

| S-EPMC8635807 | biostudies-literature
| S-EPMC4960557 | biostudies-literature
2023-02-28 | GSE198406 | GEO
| S-EPMC7055236 | biostudies-literature
| S-EPMC2848978 | biostudies-literature
| S-EPMC5447385 | biostudies-literature
| S-EPMC5722519 | biostudies-other
| S-EPMC3721386 | biostudies-literature
2013-12-03 | E-GEOD-49047 | biostudies-arrayexpress
| S-EPMC2659714 | biostudies-literature