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

Ann-Christin Gnirck, Marie-Sophie Philipp, Alex Waterhölter, Malte Wunderlich, Nikhat Shaikh, Virginia Adamiak, Lena Henneken, Tobias Kautz, Tingting Xiong, Daniela Klaus, Pascal Tomczyk, Mohamad M. Al-Bahra, Dirk Menche, Mark Walkenhorst, Olivier Lantz, Anne Willing, Manuel A. Friese, Tobias B. Huber, Christian F. Krebs, Ulf Panzer, Christian Kurts () and Jan-Eric Turner ()
Additional contact information
Ann-Christin Gnirck: University Medical Center Hamburg-Eppendorf
Marie-Sophie Philipp: University Hospital Bonn
Alex Waterhölter: University Medical Center Hamburg-Eppendorf
Malte Wunderlich: University Medical Center Hamburg-Eppendorf
Nikhat Shaikh: University Medical Center Hamburg-Eppendorf
Virginia Adamiak: University Medical Center Hamburg-Eppendorf
Lena Henneken: University Medical Center Hamburg-Eppendorf
Tobias Kautz: University Medical Center Hamburg-Eppendorf
Tingting Xiong: University Medical Center Hamburg-Eppendorf
Daniela Klaus: University Hospital Bonn
Pascal Tomczyk: University of Bonn
Mohamad M. Al-Bahra: University of Bonn
Dirk Menche: University of Bonn
Mark Walkenhorst: University Medical Center Hamburg-Eppendorf
Olivier Lantz: Inserm U932, Laboratoire d’immunologie Clinique and Centre d’investigation Clinique en Biothérapie Gustave-Roussy, Institut Curie
Anne Willing: University Medical Center Hamburg-Eppendorf
Manuel A. Friese: University Medical Center Hamburg-Eppendorf
Tobias B. Huber: University Medical Center Hamburg-Eppendorf
Christian F. Krebs: University Medical Center Hamburg-Eppendorf
Ulf Panzer: University Medical Center Hamburg-Eppendorf
Christian Kurts: University Hospital Bonn
Jan-Eric Turner: University Medical Center Hamburg-Eppendorf

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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-MAITCAST 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.

Date: 2023
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DOI: 10.1038/s41467-023-43269-0

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