Dataset Information

Fisetin ameliorates acute colitis in mice via gut microbiota associated linoleic acid metabolism to regulate Th17/Treg balance

ABSTRACT:

This study investigated the therapeutic effects of FST on colitis in mice by exploring its impact on the gut microbiota, metabolites, and immune response. The results show FST alleviated colitis in mice, including mitigated weight loss, improved colon length shortening, and reduced mRNA expression of inflammatory factors (IL-6, TNF-α, IL-1β), while restoring the disrupted Th17/Treg balance in mesenteric lymph nodes, spleen, and colon tissues. 16S rRNA sequencing revealed gut microbiota dysbiosis in colitis mice, characterized by reduced abundance of Bacteroidota and Bifidobacterium. FST treatment markedly restored the balance among these genera, improving the gut microbiota dysbiosis. Particularly, FST enriched Bifidobacterium in colitis mice. Untargeted metabolomics analysis indicated FST altered downstream metabolite expression of Bifidobacterium, reducing LA level and increasing CLA level. RNA-seq revealed that CLA can regulate the PI3K-AKT signaling pathway. CLA inhibits the phosphorylation of PI3K, AKT, and mTOR proteins, thereby suppressing Th17 cells differentiation and promoting Treg cells differentiation.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS13284 | MetaboLights | 2025-12-03

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS13284_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS13284_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13284_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13284_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 6

Similar Datasets

Project description:Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the interleukin-4 receptor alpha chain (IL-4RÎ±-R576) biases induced Treg (iTreg) cells towards a T helper 17 (TH17) cell fate. This skewing reflects the recruitment by IL-4RÎ±-R576 of the adaptor protein growth factor receptor-bound protein 2 (GRB2), which drives IL-17 expression by an extracellular signal-regulated kinase-, IL-6- and STAT3-dependent mechanism. We showed that the IL-4RÎ±-R576 mutation elicits TH17 airway responses in vivo, in a house dust mite (HDM)- or ovalbumin (OVA)-driven model of airway inflammation in the mice carry the IL-4RÎ±-R576 mutation (Il4raR576 mice). Treg cell-specific deletion of genes encoding IL-6RÎ± or the master TH17 cell regulator Retinoid-related Orphan Receptor Î³t (RORÎ³t), but not IL-4 and IL-13, protected mice against exacerbated airway inflammation induced by IL-4RÎ±--576. Analysis of lung tissue Treg cells revealed that the expression of IL-17 and the TH17 cell-associated chemokine receptor CCR6 was largely overlapping and highly enriched in Treg and conventional T (Tconv) cells of allergen-treated Il4raR576 mice. To further characterize the subset of IL-17 producing Foxp3+ Treg in the lung of OVA-treated mice we utilized CCR6 as a marker of Treg cells committed towards the TH17 cell lineage to examine their functional, epigenetic and transcriptional profiles. CCR6+Foxp3EGFP+ Treg cells isolated from OVA-sensitized and challenged Il4raR576 mice, by FACS (Fluorescence Activated Cell Sorting) exhibited decreased methylation of the Foxp3 CNS2 locus comparing to CCR6âFoxp3EGFP+ Treg cells from same animals, indicative of decreased stability. They also exhibited profoundly decreased suppressive function as compared to CCR6â WT and CCR6â Il4raR576 counterparts. Transcriptional profiling of CCR6+Foxp3EGFP+ Treg cells revealed increased relative expression in CCR6+ Il4raR576 Treg cells of genes associated with a TH17 cell signature, including Rorc, Ccr6, Il23r, Il17a, Il17f, Il1r1, Nr1d1, Cstl, and Ahr comparing to CCR6âFoxp3EGFP+ Treg cells from same animals. Three CCR6+Foxp3EGFP+ Il4raR576 replicates and four CCR6âFoxp3EGFP+ Il4raR576 Treg replicates (controls) were sampled

Project description:Carbo2013 - Cytokine driven CD4+ T Cell differentiation and phenotype plasticity CD4+ T cells can differentiate into different phenotypes depending on the cytokine milieu. Here a computational and mathematical model with sixty ordinary differential equations representing a CD4+ T cell differentiating into either Th1, Th2, Th17 or iTreg cells, has been constructed. The model includes cytokines, nuclear receptors and transcription factors that define fate and function of CD4+ T cells. Computational simulations illustrate how a proinflammatory Th17 cell can undergo reprogramming into an anti-inflammatory iTreg phenotype following PPARc activation. This model is described in the article: Systems Modeling of Molecular Mechanisms Controlling Cytokine-driven CD4+ T Cell Differentiation and Phenotype Plasticity. Carbo A, Hontecillas R, Kronsteiner B, Viladomiu M, Pedragosa M, Lu P, Philipson CW, Hoops S, Marathe M, Eubank S, Bisset K, Wendelsdorf K, Jarrah A, Mei Y, Bassaganya-Riera J PLoS Computational Biology [2013, 9(4):e1003027] Abstract: Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa. Author's comment: CD4+ T cell computational model (Version 1.4) Steady state corrected. There was a problem in the internalization of IL-17 in its mathematical function. This model is hosted on BioModels Database and identified by: MODEL1304230001 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Fisetin ameliorates acute colitis in mice via gut microbiota associated linoleic acid metabolism to regulate Th17/Treg balance

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets