The AHR repressor limits expression of antimicrobial genes but not AHR-dependent genes in intestinal eosinophils

Author:

Weighardt Heike1ORCID,Shapiro Michael2ORCID,Mayer Michelle1ORCID,Förster Irmgard1ORCID,Stockinger Brigitta2ORCID,Diny Nicola Laura23ORCID

Affiliation:

1. Immunology and Environment, Life and Medical Sciences Institute, University of Bonn , Carl-Troll-Straße 31, 53115 Bonn , Germany

2. AhR Immunity Lab, The Francis Crick Institute , 1 Midland Road, London NW1 1AT , United Kingdom

3. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Venusberg-Campus 1, 53127 Bonn , Germany

Abstract

Abstract Intestinal eosinophils express the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor that responds to dietary or environmental ligands. AHR regulates tissue adaptation, survival, adhesion, and immune functions in intestinal eosinophils. The AHR repressor (AHRR) is itself induced by AHR and believed to limit AHR activity in a negative feedback loop. We analyzed gene expression in intestinal eosinophils from wild-type and AHRR knockout mice and found that AHRR did not suppress most AHR-dependent genes. Instead, AHRR limited the expression of a distinct small set of genes involved in the innate immune response. These included S100 proteins, antimicrobial proteins, and alpha-defensins. Using bone marrow–derived eosinophils, we found that AHRR knockout eosinophils released more reactive oxygen species upon stimulation. This work shows that the paradigm of AHRR as a repressor of AHR transcriptional activity does not apply to intestinal eosinophils. Rather, AHRR limits the expression of innate immune response and antimicrobial genes, possibly to maintain an anti-inflammatory phenotype in eosinophils when exposed to microbial signals in the intestinal environment.

Funder

Francis Crick Institute

Cancer Research UK

UK Medical Research Council

Wellcome Trust

Sir Henry Wellcome Fellowship

Jürgen Manchot Foundation

Publisher

Oxford University Press (OUP)

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. The enigmatic AHRR: beyond aryl hydrocarbon receptor repression;Journal of Leukocyte Biology;2024-07-20

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