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Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation

ABSTRACT: Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin fiber diet promotes Tph1-expressing inflammatory ILC2s (ILC2INFLAM) in the colon which produce IL-5 but not tissue-protective amphiregulin (AREG), resulting in accumulation of eosinophils. This exacerbates inflammation in a murine model of intestinal damage and inflammation in an ILC2- and eosinophil-dependent manner. Mechanistically, inulin fiber diet elevated microbiota-derived bile acids, including cholic acid (CA) that induced expression of ILC2-activating IL-33. In IBD patients, bile acids, their receptor farnesoid X receptor (FXR), IL-33, and eosinophils were all upregulated compared to controls, suggesting relevance of this diet-ILC2 axis in human IBD pathogenesis. Together, these data reveal that dietary fiber-induced changes in microbial metabolites operate as a rheostat that governs protective versus pathologic ILC2 responses with relevance to precision nutrition for inflammatory diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255243 | GEO | 2024/02/12

REPOSITORIES: GEO

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Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation - Bulk RNA-Seq

Project description:Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin fiber diet promotes Tph1-expressing inflammatory ILC2s (ILC2INFLAM) in the colon which produce IL-5 but not tissue-protective amphiregulin (AREG), resulting in accumulation of eosinophils. This exacerbates inflammation in a murine model of intestinal damage and inflammation in an ILC2- and eosinophil-dependent manner. Mechanistically, inulin fiber diet elevated microbiota-derived bile acids, including cholic acid (CA) that induced expression of ILC2-activating IL-33. In IBD patients, bile acids, their receptor farnesoid X receptor (FXR), IL-33, and eosinophils were all upregulated compared to controls, suggesting relevance of this diet-ILC2 axis in human IBD pathogenesis. Together, these data reveal that dietary fiber-induced changes in microbial metabolites operate as a rheostat that governs protective versus pathologic ILC2 responses with relevance to precision nutrition for inflammatory diseases.

2024-02-13 | GSE255720 | GEO

Deciphering the combinatorial influence of diet and the microbiota on experimental colitis

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RNA-seq of liver from Ldlr-/- mouse fed with inulin or cellulose supplemented atherogenic diet

Project description:Dietary fiber such as inulin have been reported to promote cardiovascular and metabolic health. However, the mechanisms involved are not well understood. We studied effects of inulin on lipid metabolism in Ldlr deficient atherosclerosis mouse model using lipidomics and transcriptomics. Plasma and tissues were collected at 10 days and/or 12 weeks after feeding an atherogenic diet supplemented with inulin or cellulose (control).

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Modulating the gut microbiota by dietary guar gum protects against diet-induced obesity but promotes non-alcoholic steatohepatitis in mice

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Cecum and liver gene expression profiles in response to dietary fibre

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2018-10-01 | GSE106375 | GEO

Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice

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2021-11-23 | E-MTAB-11094 | biostudies-arrayexpress

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Project description:ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue. ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.

2013-12-31 | E-GEOD-45458 | biostudies-arrayexpress

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Project description:Group 2 innate lymphoid cells (ILC2) are enriched in colonic tissues, but their precise role under intestinal inflammation, including inflammatory bowel disease (IBD) other than helminth infection, is poorly understood. Here, we analysed global gene expression of colonic ILC2 in healthy and colitis mice and found that type I interferon (T1IFN)-stimulated genes (ISGs) are enriched in ILC2 under DSS-induced colitis. Enhancement of T1IFN signaling in ILC2 under DSS-induced colitis were correlated to downregulation in cytokine production of ILC2, such as IL-5. Blocking T1IFN signaling during colitis resulted in exaggeration of colitis both in wild-type and Rag2-deficient mice. Collectively, these findings show the potential roles of T1IFN in ILC2 contributing to the development of colitis.

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