Interleukin-10 inhibits important components of trained immunity in human monocytes
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Le résumé fourni par la source
Trained immunity induces antigen-agnostic enhancement of host defense and protection against secondary infections, but inappropriate activation can contribute to the pathophysiology of inflammatory diseases. Tight regulation of trained immunity is therefore needed to avoid pathology, but little is known about the endogenous processes that modulate it. Here, we investigated the potential of interleukin (IL)-10, a prototypical anti-inflammatory cytokine, to inhibit trained immunity. IL-10 induced tolerance and inhibited trained immunity in primary human monocytes at both functional and transcriptional levels. Inhibition of STAT3, a signaling route that mediates IL-10 signals, induced trained immunity. IL-10 downregulated glycolytic and oxidative metabolism in monocytes but did not impact the metabolic effects of β-glucan-induced trained immunity. Furthermore, IL-10 prevented increased reactive oxygen species production in Bacillus Calmette-Guérin (BCG)-induced training but did not influence phagocytosis upregulation. In a cohort study of healthy volunteers vaccinated with BCG, genetic variants that influenced IL-10 or its receptor modulated BCG-induced trained immunity. Furthermore, circulating IL-10 concentrations were negatively correlated with induction of trained immunity after BCG vaccination in a sex-specific manner. In conclusion, IL-10 inhibited several, albeit not all, immunological functions amplified after induction of trained immunity. Follow-up studies should explore the precise molecular mechanism that mediates the effects of IL-10 on trained immunity. Addressing these knowledge gaps is an important step toward optimizing IL-10's potential as a therapeutic target in diseases characterized by inappropriate induction of trained immunity.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Interleukin-10 inhibits important components of trained immunity in human monocytes
- Date Crossref
- 12/11/2024
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Royal Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Department of Internal Medicine and Radboud Center for Infectious Diseases pays non établi dans la noticeÉtablissement de santé
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Radboud University Medical Center pays non établi dans la noticeOrganisme public
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Murdoch Children's Research Institute Inflammatory Origins Group pays non établi dans la noticeOrganisation à but non lucratif
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Rotterdam University of Applied Sciences Research Centre Innovations in Care pays non établi dans la noticeUniversité ou école supérieure
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Iuliu Hațieganu University of Medicine and Pharmacy Department of Medical Genetics pays non établi dans la noticeUniversité ou école supérieure
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University of Bonn Department of Immunology and Metabolism pays non établi dans la noticeUniversité ou école supérieure
Royal Children's Hospital, Radboud University Nijmegen et Department of Internal Medicine and Radboud Center for Infectious Diseases — University Medical Center, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.