The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Diny, Nicola L.; Schonfeldova, Barbora; Shapiro, Michael; Winder, Matthew L.; Varsani-Brown, Sunita; Stockinger, Brigitta

doi:10.1084/jem.20210970

Cited by 36 publications

(52 citation statements)

References 102 publications

(130 reference statements)

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“…AHR drove expression of Clec4a4 as well as other immunomodulatory molecules, such as DPEP2 and PD-L1. A very recent study independently corroborated that eosinophils of the gastrointestinal tract display an AHR-dependent profile ( 51 ). In the gut, AHR is activated by indoles derived from vegetables that contain tryptophan catabolic products ( 38 – 42 ) and microbial degradation of nutritional tryptophan ( 47 ).…”

Section: Discussionmentioning

confidence: 85%

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

Wang

Kasamatsu

Joshita

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Eosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4 + eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. Selective AHR deletion in eosinophils depleted Clec4a4 + eosinophils, augmented innate lymphocytes producing type 2 cytokines, and enhanced helminth clearance. We conclude that Clec4a4 + eosinophils have immunomodulatory functions, which could be harnessed for the therapy of food allergies and eosinophilic gastrointestinal disorders.

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Section: Discussionmentioning

confidence: 85%

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

Wang

Kasamatsu

Joshita

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Activation of AhR contributes to tissue adaptation of intestinal eosinophils in mice. Exposure to BaP signi cantly enhances IL-8 secretion by human eosinophilic leukemia cell line in vitro 27 . However, the relationship between AhR activation and basophils was not established.…”

Section: Discussionmentioning

confidence: 97%

Unbalanced aryl hydrocarbon receptor expression in peripheral and lesional T cell subsets of atopic dermatitis

Yong-fang

Zhao

Zhang

2022

Preprint

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Conclusion AhR was highly expressed in subpopulations of T cells in peripheral blood and skin lesions of AD, suggesting that AhR might contribute to the pathogenesis of AD. Background and Objective The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is involved in the pathogenesis of a variety of skin diseases such as atopic dermatitis (AD). In this study, we aimed to study the AhR-expressing cells in T helper 17 (Th17), T helper 22 (Th22), regulatory T cells (Treg) and B cells in peripheral blood and in AD skin lesions. Methods Twenty AD patients defined according to the Chinese criteria of atopic dermatitis and eighteen healthy subjects were included in our study. The AhR-expressing Th17, Th22, Treg and total B cells in peripheral blood was measured by flow cytometry. The AhR+ Th17 cells and AhR+ Th22 cells in AD skin lesions was measured by immunofluorescence. The mRNA of AhR, interleukin (IL)-22, IL-17A, IL-10, Foxp3, RORγT and TGF-β in peripheral blood mononuclear cells (PBMCs) was measured by real-time quantitative polymerase chain reaction. Results The expression of AhR in peripheral CD4+ T cells, Th22 cells, Treg cells and total B cells was significantly increased in AD. AhR+IL-17A+ and AhR+IL-22+ lymphocytes were also increased in AD skin lesions. The mRNA levels of AhR, IL-22 and IL-17A in PBMCs in AD patients were significantly higher. AhR mRNA levels in PBMCs positively correlated with peripheral basophil count, peripheral eosinophils count and mRNA levels of IL-22.

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“…These cells in the peritoneal intestine and pleura are essential for antibacterial response in infancy and old age when the immune system is developing or declining. It was recently described by Diny et al [ 95 ] that AhR controlled longevity, tissue adaptation and functions of eosinophils, and gene expression in the small intestine.…”

Section: Pesticide-induced Dysbiosis May Be Associated With Ahr Signa...mentioning

confidence: 99%

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

Lima

Falcão

Rosa

et al. 2022

IJMS

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The environmental and occupational risk we confront from agricultural chemicals increases as their presence in natural habitats rises to hazardous levels, building a major part of the exposome. This is of particular concern in low- and middle-income countries, such as Brazil, known as a leading producer of agricultural commodities and consumer of pesticides. As long as public policies continue to encourage the indiscriminate use of pesticides and governments continue to support this strategy instead of endorsing sustainable agricultural alternatives, the environmental burden that damages epithelial barriers will continue to grow. Chronic exposure to environmental contaminants in early life can affect crucial barrier tissue, such as skin epithelium, airways, and intestine, causing increased permeability, leaking, dysbiosis, and inflammation, with serious implications for metabolism and homeostasis. This vicious cycle of exposure to environmental factors and the consequent damage to the epithelial barrier has been associated with an increase in immune-mediated chronic inflammatory diseases. Understanding how the harmful effects of pesticides on the epithelial barrier impact cellular interactions mediated by endogenous sensors that coordinate a successful immune system represents a crucial challenge. In line with the epithelial barrier hypothesis, this narrative review reports the available evidence on the effects of pesticides on epithelial barrier integrity, dysbiosis, AhR signaling, and the consequent development of immune-mediated inflammatory diseases.

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The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Cited by 36 publications

References 102 publications

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

Unbalanced aryl hydrocarbon receptor expression in peripheral and lesional T cell subsets of atopic dermatitis

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

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The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice

Cited by 36 publications

References 102 publications

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+eosinophils unique to the small intestine

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+eosinophils unique to the small intestine

Unbalanced aryl hydrocarbon receptor expression in peripheral and lesional T cell subsets of atopic dermatitis

Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

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The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine