Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease.

Autor: Gnirck AC; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Euroimmun, Lübeck, Germany., Philipp MS; Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany.; Division of Immunology, Paul-Ehrlich-Institut Langen, Langen, Germany., Waterhölter A; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Wunderlich M; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Shaikh N; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Adamiak V; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Henneken L; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kautz T; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institut für Transfusionsmedizin, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Xiong T; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Klaus D; Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany., Tomczyk P; Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany., Al-Bahra MM; Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany., Menche D; Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany., Walkenhorst M; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lantz O; Inserm U932, Laboratoire d'immunologie Clinique and Centre d'investigation Clinique en Biothérapie Gustave-Roussy, Institut Curie, Paris, France., Willing A; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Friese MA; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Huber TB; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Krebs CF; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Panzer U; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kurts C; Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany. ckurts@uni-bonn.de.; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia. ckurts@uni-bonn.de., Turner JE; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.turner@uke.de.; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.turner@uke.de.; Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.turner@uke.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 15; Vol. 14 (1), pp. 7372. Date of Electronic Publication: 2023 Nov 15.
DOI: 10.1038/s41467-023-43269-0
Abstrakt: Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAIT CAST mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-β. Interactome analysis predicts CXCR6 - CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6 + MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.
(© 2023. The Author(s).)
Databáze: MEDLINE
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