Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells

This study aimed to examine whether probiotics, which suppressed the differentiation of splenic T cells into type 2 helper T (Th2) cells and induced into regulatory T cells in vitro, alleviate allergic rhinitis (AR) and gut microbiota disturbance. We isolated Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 from human faecal microbiota and kimchi, respectively, and examined their effects on ovalbumin (OVA)-induced AR and gut microbiota disturbance in mice. Treatment with IM55, IM76, or their probiotic mixture (PM) significantly reduced OVA-induced allergic nasal symptoms and blood immunoglobulin E (IgE) levels in mice. These also reduced OVA-induced interleukin (IL)-4 and IL-5 levels in nasal tissues and bronchoalveolar lavage fluid (BALF) but increased OVA-suppressed IL-10 levels. Treatment with IM55, IM76, or PM reduced OVA-induced increase in the populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of regulatory T cells in the BALF. Treatment with IM55, IM76, or PM also inhibited OVA-induced expression of IL-5 in lung and colon tissues and restored OVA-disturbed composition of gut microbiota Proteobacteria, Bacteroidetes, and Actinobacteria. These results suggest that IM55 and IM67 can alleviate AR by restoring Th2/Treg imbalance and gut microbiota disturbance.

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The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz170 ◽

2019 ◽

Vol 14 (4) ◽

pp. 508-524 ◽

Cited By ~ 1

Author(s):

Heike Schmitt ◽

Julia Ulmschneider ◽

Ulrike Billmeier ◽

Michael Vieth ◽

Patrizio Scarozza ◽

...

Keyword(s):

Ulcerative Colitis ◽

Wound Healing ◽

T Cells ◽

Regulatory T Cells ◽

Th17 Cells ◽

Experimental Colitis ◽

Foxp3 Expression ◽

Treg Cells ◽

Tlr9 Agonist ◽

Anti Inflammatory

Abstract Background and Aims The topically applied Toll-like receptor 9 [TLR9] agonist cobitolimod is a first-in-class DNA-based oligonucleotide with demonstrated therapeutic efficacy in clinical trials with ulcerative colitis [UC] patients. We here characterized its anti-inflammatory mechanism in UC. Methods Luminal cobitolimod administration was evaluated in an experimental dextran sodium sulfate [DSS]-induced colitis model. Cultured blood and mucosal cells from UC patients were treated with cobitolimod and analysed via microarray, quantitative real-time PCR, ELISA and flow cytometry. Intestinal slides of cobitolimod-treated UC patients were analysed by immunohistochemistry. Results Cobitolimod administration markedly suppressed experimental colitis activity, and microarray analyses demonstrated mucosal IL10 upregulation and suppression of IL17 signalling pathways. Cobitolimod treatment was associated with significant induction of mucosal IL10+Tr1 and Treg cells and suppression of Th17 cells. TLR9 knockout mice indicated that cobitolimod requires TLR9 signalling for IL10 induction. In UC patients, mucosal TLR9 levels correlated with severity of inflammation. Cobitolimod inhibited IL17A and IL17F, but increased IL10 and FoxP3 expression in cultured intestinal UC T cells. Cobitolimod-mediated suppression of intestinal IL17+T cells was abrogated by IL10 blockade. Furthermore, cobitolimod led to heightened IL10 production by wound healing macrophages. Immunohistochemistry in intestinal biopsies of cobitolimod-treated UC patients indicated increased presence of IL10+mononuclear and regulatory T cells, as well as reduction of IL17+cells. Conclusion Activation of TLR9 via cobitolimod might represent a novel therapeutic approach in UC, as it suppresses Th17 cells and induces anti-inflammatory IL10+macrophages and regulatory T cells, thereby modifying the dysregulated intestinal cytokine balance. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

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Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice

BMC Immunology ◽

10.1186/1471-2172-9-65 ◽

2008 ◽

Vol 9 (1) ◽

pp. 65 ◽

Cited By ~ 125

Author(s):

Tomas Hrncir ◽

Renata Stepankova ◽

Hana Kozakova ◽

Tomas Hudcovic ◽

Helena Tlaskalova-Hogenova

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Gut Microbiota ◽

Germ Free

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Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis

Nature Communications ◽

10.1038/s41467-017-01917-2 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 46

Author(s):

Xiaomin Yao ◽

Chenhong Zhang ◽

Yue Xing ◽

Guang Xue ◽

Qianpeng Zhang ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Gut Microbiota

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Bifidobacterium infantis Potentially Alleviates Shrimp Tropomyosin-Induced Allergy by Tolerogenic Dendritic Cell-Dependent Induction of Regulatory T Cells and Alterations in Gut Microbiota

Frontiers in Immunology ◽

10.3389/fimmu.2017.01536 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 27

Author(s):

Linglin Fu ◽

Jinyu Song ◽

Chong Wang ◽

Shujie Fu ◽

Yanbo Wang

Keyword(s):

T Cells ◽

Dendritic Cell ◽

Regulatory T Cells ◽

Gut Microbiota ◽

Bifidobacterium Infantis ◽

Tolerogenic Dendritic Cell

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Enhanced Susceptibility of Galectin-1 Deficient Mice to Experimental Colitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.687443 ◽

2021 ◽

Vol 12 ◽

Author(s):

Raquel Fernandez-Perez ◽

Mercedes Lopez-Santalla ◽

Rebeca Sánchez-Domínguez ◽

Omaira Alberquilla ◽

Irene Gutiérrez-Cañas ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Inflammatory Response ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Cell Trafficking ◽

Wild Type ◽

Cell Reactivity ◽

Deficient Mice

Galectin-1 is a β-galactoside-binding lectin, ubiquitously expressed in stromal, epithelial, and different subsets of immune cells. Galectin-1 is the prototype member of the galectin family which shares specificity with β-galactoside containing proteins and lipids. Immunomodulatory functions have been ascribed to endogenous galectin-1 due to its induction of T cell apoptosis, inhibitory effects of neutrophils and T cell trafficking. Several studies have demonstrated that administration of recombinant galectin-1 suppressed experimental colitis by modulating adaptive immune responses altering the fate and phenotype of T cells. However, the role of endogenous galectin-1 in intestinal inflammation is poorly defined. In the present study, the well-characterized acute dextran sulfate sodium (DSS)-induced model of ulcerative colitis was used to study the function of endogenous galectin-1 during the development of intestinal inflammation. We found that galectin-1 deficient mice (Lgals1−/− mice) displayed a more severe intestinal inflammation, characterized by significantly elevated clinical scores, than their wild type counterparts. The mechanisms underlying the enhanced inflammatory response in colitic Lgals1−/− mice involved an altered Th17/Th1 profile of effector CD4+ T cells. Furthermore, increased frequencies of Foxp3+CD4+ regulatory T cells in colon lamina propria in Lgals1−/− mice were found. Strikingly, the exacerbated intestinal inflammatory response observed in Lgals1−/− mice was alleviated by adoptive transfer of wild type Foxp3+CD4+ regulatory T cells at induction of colitis. Altogether, these data highlight the importance of endogenous galectin-1 as a novel determinant in regulating T cell reactivity during the development of intestinal inflammation.

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