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  1. Article ; Online: The aryl hydrocarbon receptor (AHR) repressor limits expression of antimicrobial genes but not AHR-dependent genes in intestinal eosinophils.

    Weighardt, Heike / Shapiro, Michael / Mayer, Michelle / Förster, Irmgard / Stockinger, Brigitta / Diny, Nicola Laura

    Journal of leukocyte biology

    2024  

    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 ... ...

    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 analysed gene expression in intestinal eosinophils from WT and AHRR-KO 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-KO 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.
    Language English
    Publishing date 2024-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiae105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 603: Show issues Location:
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  2. Article ; Online: The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice.

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

    The Journal of experimental medicine

    2022  Volume 219, Issue 4

    Abstract: Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and ... ...

    Abstract Eosinophils are potent sources of inflammatory and toxic mediators, yet they reside in large numbers in the healthy intestine without causing tissue damage. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response, cell-cell communication, extracellular matrix remodeling, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis. Eosinophils from AHR-deficient mice failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. AHR-deficient eosinophils were functionally impaired in the adhesion to and degradation of extracellular matrix, were more prone to degranulation, and had an extended life span. Lack of AHR in eosinophils had wider effects on the intestinal immune system, affecting the T cell compartment in nave and helminth-infected mice. Our study demonstrates that the response to environmental triggers via AHR partially shapes tissue adaptation of eosinophils in the small intestine.
    MeSH term(s) Animals ; Eosinophils/metabolism ; Homeostasis ; Intestine, Small ; Mice ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/metabolism
    Chemical Substances Receptors, Aryl Hydrocarbon
    Language English
    Publishing date 2022-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20210970
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Hypereosinophilia causes progressive cardiac pathologies in mice.

    Diny, Nicola Laura / Wood, Megan Kay / Won, Taejoon / Talor, Monica Vladut / Lukban, Clarisse / Bedja, Djahida / Wang, Nadan / Kalinoski, Hannah / Daoud, Abdel / Talbot, C Conover / Leei Lin, Brian / Čiháková, Daniela

    iScience

    2023  Volume 26, Issue 10, Page(s) 107990

    Abstract: Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue ... ...

    Abstract Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca
    Language English
    Publishing date 2023-09-21
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.107990
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Dietary environmental factors shape the immune defense against Cryptosporidium infection.

    Maradana, Muralidhara Rao / Marzook, N Bishara / Diaz, Oscar E / Mkandawire, Tapoka / Diny, Nicola Laura / Li, Ying / Liebert, Anke / Shah, Kathleen / Tolaini, Mauro / Kváč, Martin / Stockinger, Brigitta / Sateriale, Adam

    Cell host & microbe

    2023  Volume 31, Issue 12, Page(s) 2038–2050.e4

    Abstract: Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or ... ...

    Abstract Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. Although it is known from human cases and animal models that CD4
    MeSH term(s) Child ; Humans ; Mice ; Animals ; Cryptosporidiosis/parasitology ; CD8-Positive T-Lymphocytes ; Cryptosporidium ; Ligands ; Diet
    Chemical Substances Ligands
    Language English
    Publishing date 2023-12-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2023.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6578: Show issues Location:
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