Exposure to p40 in Early Life Prevents Intestinal Inflammation in Adulthood Through Inducing a Long-Lasting Epigenetic Imprint on TGFβSummary
| Autor: | Oliver G. McDonald, M. Kay Washington, Fang Yan, Yilin Deng, Anna L. Means, D. Brent Polk, Sari Acra, Richard M. Peek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment H3K4me histone H3 on the lysine 4 methylation Probiotic Function Factor RC799-869 LGG Lactobacillus rhamnosus GG IEC intestinal epithelial cell Epigenesis Genetic ZO-1 zonula occludens-1 Mice 0302 clinical medicine Pregnancy Transforming Growth Factor beta Gene expression TGFβ transforming growth factor β IFN-γ interferon-γ Setd1β su(var)3-9 enhancer-of-zeste and trithorax domain–containing 1β Intestinal Mucosa Original Research Histone Methyltransferase Intestinal Epithelial Cell TNF tumor necrosis factor Mice Inbred BALB C IBD inflammatory bowel disease Gastroenterology ELISA enzyme-linked immunosorbent assay Diseases of the digestive system. Gastroenterology Colitis RT-PCR reverse- transcription polymerase chain reaction mRNA messenger RNA ChIP chromatin immunoprecipitation medicine.anatomical_structure Prenatal Exposure Delayed Effects Histone methyltransferase shRNA short hairpin RNA Female 030211 gastroenterology & hepatology medicine.symptom Regulatory T cell Treg regulatory T cell Mice Transgenic Inflammation Biology Regulatory T Cell 03 medical and health sciences Histone H3 FBS fetal bovine serum DSS dextran sulfate sodium medicine Animals Epigenetics SV40 simian virus 40 Hepatology Probiotics Growth factor TNBS 2 4 6-trinitrobenzenesulfonic acid Epithelial Cells medicine.disease WT wild-type EGFR epidermal growth factor receptor IL interleukin Mice Inbred C57BL MSIE mouse small intestinal epithelial 030104 developmental biology YAMC young adult mouse colonic Cancer research |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 11, Iss 5, Pp 1327-1345 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims Colonization by gut microbiota in early life confers beneficial effects on immunity throughout the host’s lifespan. We sought to elucidate the mechanisms whereby neonatal supplementation with p40, a probiotic functional factor, reprograms intestinal epithelial cells for protection against adult-onset intestinal inflammation. Methods p40 was used to treat young adult mouse colonic (YAMC) epithelial cells with and without deletion of a methyltransferase, su(var)3-9, enhancer-of-zeste and trithorax domain–containing 1β (Setd1β), and mice in early life or in adulthood. Anti–transforming growth factor β (TGFβ)-neutralizing antibodies were administered to adult mice with and without colitis induced by 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium. We examined Setd1b and Tgfb gene expression, TGFβ production, monomethylation and trimethylation of histone H3 on the lysine 4 residue (H3K4me1/3), H3K4me3 enrichment in Tgfb promoter, differentiation of regulatory T cells (Tregs), and the inflammatory status. Results p40 up-regulated expression of Setd1b in YAMC cells. Accordingly, p40 enhanced H3K4me1/3 in YAMC cells in a Setd1β-dependent manner. p40-regulated Setd1β mediated programming the TGFβ locus into a transcriptionally permissive chromatin state and promoting TGFβ production in YAMC. Furthermore, transient exposure to p40 during the neonatal period and in adulthood resulted in the immediate increase in Tgfb gene expression. However, only neonatal p40 supplementation induced the sustained H3K4me1/3 and Tgfb gene expression that persisted into adulthood. Interfering with TGFβ function by neutralizing antibodies diminished the long-lasting effects of neonatal p40 supplementation on differentiation of Tregs and protection against colitis in adult mice. Conclusions Exposure to p40 in early life enables an epigenetic imprint on TGFβ, leading to long-lasting production of TGFβ by intestinal epithelial cells to expand Tregs and protect the gut against inflammation. Graphical abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|