The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells

Ye, Jian; Qiu, Ju; Bostick, John W.; Ueda, Aki; Schjerven, Hilde; Li, Shiyang; Jobin, Christian; Chen, Zongming E.; Zhou, Liang

doi:10.1016/j.celrep.2017.10.114

Cited by 149 publications

(145 citation statements)

References 68 publications

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that gut colonization by specific microbial communities causes induction and expansion of Foxp3 + Treg cells in the intestinal and systemic compartments. [43][44][45] Further, gut bacteria play a critical role in maintaining peripheral tolerance and gut immune homeostasis. 46,47 Our results show that depletion of gut bacteria using broad-spectrum antibiotics diminishes Foxp3 + T-cell frequency, compared with mice with an intact gut microbiota, but less significantly in YBGtreated mice compared with their control counterparts.…”

Section: Discussionmentioning

confidence: 99%

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Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

et al. 2019

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Summary The dietary supplement and prebiotic values of β‐glucan‐rich products have been widely recognized and dietary approaches for modulating autoimmunity have been increasingly explored, we assess the impact of oral administration of high‐purity yeast β‐glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non‐digestible complex polysaccharide caused a dectin‐1‐dependent immune response involving increased expression of interleukin‐10 (IL‐10), retinaldehyde dehydrogenase (Raldh) and pro‐inflammatory cytokines in the gut mucosa. YBG‐exposed intestinal dendritic cells induced/expanded primarily Foxp3+, IL‐10+ and IL‐17+ T cells, ex vivo. Importantly, prolonged oral administration of low‐dose YBG at pre‐diabetic stage suppressed insulitis and significantly delayed the appearance of T1D in non‐obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3+ T‐cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh‐substrate and β‐cell antigen, resulted in better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also an oral tolerogenic‐adjuvant‐like effect, and these features could be exploited for modulating autoimmunity in T1D.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

et al. 2019

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show abstract

“…Previous studies have shown that gut colonization by specific microbial communities causes induction and expansion of Foxp3+ Tregs in the intestinal and systemic compartments [44][45][46] .…”

Section: Discussionmentioning

confidence: 99%

Complex dietary-polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

Gudi

Pérez

Johnson

et al. 2018

Preprint

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Since the dietary supplement and prebiotic value of β -glucan-rich products have been widely recognized and the dietary approaches for modulating autoimmunity have been increasingly explored, we assessed the impact of oral administration of high-pure yeast β -glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a Dectin-1-dependent immune response involving increased expression of IL10, retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa. YBG-exposed intestinal DCs induced/expanded primarily Foxp3+, IL10+ and IL17+ T cells, ex vivo. Importantly, prolonged oral administration of low-dose YBG at pre-diabetic stage suppressed insulitis and significantly delayed the T1D incidence in non-obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3+ T cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh-substrate and β -cell antigen, resulted in a better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also has an oral tolerogenic-adjuvant-like effect, and these features could be exploited for modulating autoimmunity in T1D.

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“…Therefore, these polysaccharides are being considered as prebiotics with the ability to promote growth of specific beneficial microbial communities. Previous studies have shown that gut colonization by specific commensal microbial communities causes induction and expansion of Foxp3+ Tregs in the intestinal and systemic compartments (47)(48)(49). Further, gut bacteria play a critical role in maintaining peripheral tolerance and gut immune homeostasis (50,51).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with yeast derived complex dietary-polysaccharide leads to suppressed gut inflammation, altered microbiota composition and increased immune regulatory short-chain fatty acid production in C57BL/6 mice

Gudi

Suber

Brown

et al. 2019

Preprint

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1Background: β-Glucans (BGs), a group of complex non-digestible polysaccharides, are 2 considered to have beneficial health effects due to their immune modulatory properties and are 3 considered as dietary supplements. However, the impact of oral administration of high-pure, well-4 defined BGs on gut inflammation, and the influence of intestinal microbiota and short-chain fatty 5 acid (SCFA) on the therapeutic effect are largely unknown. 6Objectives: The aim of this study, using a mouse model of chemical induced colitis, was to 7 investigate the impact of oral administration of high-pure yeast BG (YBG) on the susceptibility to 8 colitis, gut immune function, and structure and function of microbiota. 9Methods: To determine the impact of oral administration of YBG on colitis susceptibility, eight 10week old C57BL/6 (B6) mice were pre-treated with YBG (250 g/mouse/day) and given dextran 11 sulfate sodium (DSS) in drinking water (2.5% w/v) and examined for the symptoms and features 12 of colitis. To assess the effect of oral administration of YBG on gut mucosa and microbiota 13 structure and function, and gut immune regulation, we determined the microbiota composition, 14 fecal SCFA levels, and intestinal T cell phenotype and cytokine secretion. The role of gut 15 microbiota in YBG treatment induced modulation of gut inflammation and immune function were 16 determined in B6 mice treated with broad-spectrum antibiotic cocktail (1 g/L ampicillin, 0.5 g/L 17 vancomycin, 1 g/L neomycin, and 1 g/L metronidazole) in drinking water. 18Results Compared to untreated mice, B6 mice that received prolonged pre-treatment with YBG 19 showed diminished severity of different features of DSS-induced colitis including overall loss of 20 body weight (P<0.001), shortening of colon (P=0.016) and histopathology (P=0.01). However, 21 high-pure YBG has no beneficial effect in terms of suppressing colitis severity when consumed 22 only during the disease stage. Compared to untreated controls, YBG pre-treated mice showed 23 42 Immunological assays and qPCR 132Cells from the small intestinal lamina propria (SiLP), large intestinal lamina propria (LiLP) and 133 mesenteric lymph node (MLN) were examined for immune cell phenotype and/or cytokine profiles 134 by FACS and multiplex assay respectively as described in our recent reports (29, 30, 33). Briefly: 135 for determining Treg frequencies, freshly isolated cells were stained for CD4 and Foxp3. For 136 determining cytokine positive T cells frequencies, cells were cultured in the presence or PMA, 137Ionomycin and Brefeldin A for 4 h, before staying for CD4 and intracellular cytokines. For 138

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The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells

Cited by 149 publications

References 68 publications

Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

Complex dietary-polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes

Pretreatment with yeast derived complex dietary-polysaccharide leads to suppressed gut inflammation, altered microbiota composition and increased immune regulatory short-chain fatty acid production in C57BL/6 mice

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