Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury
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Le résumé fourni par la source
Glucocorticoids remain a cornerstone of therapeutic regimes for autoimmune and chronic inflammatory diseases - for example, in different forms of crescentic glomerulonephritis - because of their rapid antiinflammatory effects, low cost, and wide availability. Despite their routine use for decades, the underlying cellular mechanisms by which steroids exert their therapeutic effects need to be fully elucidated. Here, we demonstrate that high-dose steroid treatment rapidly reduced the number of proinflammatory CXCR3+CD4+ T cells in the kidney by combining high-dimensional single-cell and morphological analyses of kidney biopsies from patients with antineutrophil cytoplasmic antibody-associated (ANCA-associated) crescentic glomerulonephritis. Using an experimental model of crescentic glomerulonephritis, we show that the steroid-induced decrease in renal CD4+ T cells is a consequence of reduced T cell recruitment, which is associated with an ameliorated disease course. Mechanistic in vivo and in vitro studies revealed that steroids act directly on renal tissue cells, such as tubular epithelial cells, but not on T cells, which resulted in an abolished renal expression of CXCL9 and CXCL10 as well as in the prevention of CXCR3+CD4+ T cell recruitment to the inflamed kidneys. Thus, we identified the CXCL9/CXCL10-CXCR3 axis as a previously unrecognized cellular and molecular target of glucocorticoids providing protection from immune-mediated pathology.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury
- Date Crossref
- 10/01/2023
- Éditeur
- American Society for Clinical Investigation
- 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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Universität Hamburg pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Hamburg-Eppendorf III. Department of Medicine pays non établi dans la noticeÉtablissement de santé
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MSH Medical School Hamburg – University of Applied Sciences and Medical University pays non établi dans la noticeUniversité ou école supérieure
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Arkana Laboratories pays non établi dans la noticeStructure de recherche
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Division of Translational Immunology pays non établi dans la noticeInstitution
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Institute of Medical Systems Biology pays non établi dans la noticeStructure de recherche
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Institute of Experimental Immunology and Hepatology pays non établi dans la noticeStructure de recherche
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Institute of Pathology pays non établi dans la noticeStructure de recherche
Universität Hamburg, III. Department of Medicine — University Medical Center Hamburg-Eppendorf et MSH Medical School Hamburg – University of Applied Sciences and Medical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.