Aryl hydrocarbon receptor activation alleviates dextran sodium sulfate-induced colitis through enhancing the differentiation of goblet cells

Yin, Jiuheng; Yang, Kunqiu; Zhou, Chao; Xu, Pan; Xiao, Weidong; Yang, Hua

doi:10.1016/j.bbrc.2019.04.136

Cited by 25 publications

(22 citation statements)

References 22 publications

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“…It was also found that FICZ reduced the protein expression of active β-catenin in organoids derived from small intestinal crypts (perhaps due to a loss of morphogenetic factors produced from crypt Paneth cells) though increased the gene expression of the transcription factor ATOH1, which promotes the differentiation of secretory lineages from ISCs, as well as altered the gene expression of other morphogenetic pathway markers (61). Though no changes in GC number were observed following FICZ administration, the observed increase of ATOH1 expression highlights the putative role of FICZ in promoting the differentiation of GCs as previously shown (52). In all, these findings suggest that KN promotes the differentiation of GCs in tandem with AhR activation but that these actions may be dependent on additional local factors such as other amino acids.…”

Section: The Contribution Of Ahr Ligands To Isc Homeostasis Tryptophasupporting

confidence: 69%

“…At present, the extent to which AhR activation works in tandem with SHP2-MAPK/ERK signaling to promote intestinal homeostasis remains largely unknown; however, its role in potentiating MAPK/ERK signals must be highlighted. Independent of SHP2, AhR activation by the tryptophan derivative 6-formylindolo (3, 2-b) carbazole (FICZ) has indeed shown to ameliorate DSS-induced colitis and exclusively promote the MAPK/ERK-dependent differentiation of GCs (52). Importantly, this selectivity for GCs occurs in parallel with a suppression of Notch signals as indicated by a down-regulation of the Notch intracellular domain (NICD) which is released upon Notch activation ( Figure 1B).…”

Section: Egfr-mapk/erk and Notchmentioning

confidence: 99%

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Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands

Wisniewski

Nagarkatti

2021

Front. Immunol.

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Maintenance of intestinal homeostasis requires the integration of immunological and molecular processes together with environmental, diet, metabolic and microbial cues. Key to this homeostasis is the proper functioning of epithelial cells originating from intestinal stem cells (ISCs). While local factors and numerous molecular pathways govern the ISC niche, the conduit through which these processes work in concordance is the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, whose role in immunoregulation is critical at barrier surfaces. In this review, we discuss how AhR signaling is emerging as one of the critical regulators of molecular pathways involved in epithelial cell renewal. In addition, we examine the putative contribution of specific AhR ligands to ISC stemness and epithelial cell fate.

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Section: The Contribution Of Ahr Ligands To Isc Homeostasis Tryptophasupporting

confidence: 69%

Section: Egfr-mapk/erk and Notchmentioning

confidence: 99%

Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands

Wisniewski

Nagarkatti

2021

Front. Immunol.

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“…Similarly, indole-3-ethanol, indole-3-pyruvate and indole-3-ethanol protect against increased gut permeability in a murine DSS-induced colitis model ( 195 ). AhR maintain intestinal permeability, with Ficz promoting goblet cell differentiation through AhR-pErk1/2 signaling pathway, and ameliorating DSS-induced colitis ( 197 ). Furthermore, after intestinal reperfusion ischemia and hypoxia, AhR activation increases Notch1 signaling, thus reducing epithelial barrier dysfunction in vivo and in vitro ( 198 ).…”

Section: Bacterial Catabolites As Aryl Hydrocarbon Receptor (Ahr) Ligands: Key Role In Gut Microbiota and Immunitymentioning

confidence: 99%

Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation

2021

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The diverse and dynamic microbial community of the human gastrointestinal tract plays a vital role in health, with gut microbiota supporting the development and function of the gut immune barrier. Crosstalk between microbiota-gut epithelium and the gut immune system determine the individual health status, and any crosstalk disturbance may lead to chronic intestinal conditions, such as inflammatory bowel diseases (IBD) and celiac disease. Microbiota-derived metabolites are crucial mediators of host-microbial interactions. Some beneficially affect host physiology such as short-chain fatty acids (SCFAs) and secondary bile acids. Also, tryptophan catabolites determine immune responses, such as through binding to the aryl hydrocarbon receptor (AhR). AhR is abundantly present at mucosal surfaces and when activated enhances intestinal epithelial barrier function as well as regulatory immune responses. Exogenous diet-derived indoles (tryptophan) are a major source of endogenous AhR ligand precursors and together with SCFAs and secondary bile acids regulate inflammation by lowering stress in epithelium and gut immunity, and in IBD, AhR expression is downregulated together with tryptophan metabolites. Here, we present an overview of host microbiota-epithelium- gut immunity crosstalk and review how microbial-derived metabolites contribute to host immune homeostasis. Also, we discuss the therapeutic potential of bacterial catabolites for IBD and celiac disease and how essential dietary components such as dietary fibers and bacterial tryptophan catabolites may contribute to intestinal and systemic homeostasis.

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“…Similar results were obtained in another study [ 20 ], and in their comparable investigation, Zelante and coworkers demonstrated that administration of IAl (18 mg/kg daily for 12 days) to mice ameliorated DSS-induced colitis [ 48 ]. In fact, there are nine more reports that FICZ protects against bacterial infections and colitis caused by T-cell transfer, DSS or TNBS [ 29 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ], with only one study observing no protection against TNBS-induced colitis [ 12 ]. When Qiu and colleagues injected mice intraperitoneally with 0.5 µg FICZ for 6 days, IL-22-producing ILCs accumulated both in the large intestine (LI) and, especially, in the SI [ 19 ].…”

Section: The Mechanism(s) By Which Ficz Il-22 and Butyrate Promotmentioning

confidence: 99%

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

Rannug

2020

IJMS

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Ever since the 1970s, when profound immunosuppression caused by exogenous dioxin-like compounds was first observed, the involvement of the aryl hydrocarbon receptor (AHR) in immunomodulation has been the focus of considerable research interest. Today it is established that activation of this receptor by its high-affinity endogenous ligand, 6-formylindolo[3,2-b]carbazole (FICZ), plays important physiological roles in maintaining epithelial barriers. In the gut lumen, the small amounts of FICZ that are produced from L-tryptophan by microbes are normally degraded rapidly by the inducible cytochrome P4501A1 (CYP1A1) enzyme. This review describes how when the metabolic clearance of FICZ is attenuated by inhibition of CYP1A1, this compound passes through the intestinal epithelium to immune cells in the lamina propria. FICZ, the level of which is thus modulated by this autoregulatory loop involving FICZ itself, the AHR and CYP1A1, plays a central role in maintaining gut homeostasis by potently up-regulating the expression of interleukin 22 (IL-22) by group 3 innate lymphoid cells (ILC3s). IL-22 stimulates various epithelial cells to produce antimicrobial peptides and mucus, thereby both strengthening the epithelial barrier against pathogenic microbes and promoting colonization by beneficial bacteria. Dietary phytochemicals stimulate this process by inhibiting CYP1A1 and causing changes in the composition of the intestinal microbiota. The activity of CYP1A1 can be increased by other microbial products, including the short-chain fatty acids, thereby accelerating clearance of FICZ. In particular, butyrate enhances both the level of the AHR and CYP1A1 activity by stimulating histone acetylation, a process involved in the daily cycle of the FICZ/AHR/CYP1A1 feedback loop. It is now of key interest to examine the potential involvement of FICZ, a major physiological activator of the AHR, in inflammatory disorders and autoimmunity.

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Aryl hydrocarbon receptor activation alleviates dextran sodium sulfate-induced colitis through enhancing the differentiation of goblet cells

Cited by 25 publications

References 22 publications

Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands

Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands

Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation

How the AHR Became Important in Intestinal Homeostasis—A Diurnal FICZ/AHR/CYP1A1 Feedback Controls Both Immunity and Immunopathology

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