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

Author

Listed:
  • Ann-Christin Gnirck

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    Euroimmun)

  • Marie-Sophie Philipp

    (University Hospital Bonn
    Division of Immunology, Paul-Ehrlich-Institut Langen)

  • Alex Waterhölter

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Malte Wunderlich

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Nikhat Shaikh

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Virginia Adamiak

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Lena Henneken

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Tobias Kautz

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Tingting Xiong

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    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
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Christian F. Krebs

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Ulf Panzer

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

  • Christian Kurts

    (University Hospital Bonn
    University of Melbourne)

  • Jan-Eric Turner

    (University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf
    University Medical Center Hamburg-Eppendorf)

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.

Suggested Citation

  • Ann-Christin Gnirck & Marie-Sophie Philipp & Alex Waterhölter & Malte Wunderlich & Nikhat Shaikh & Virginia Adamiak & Lena Henneken & Tobias Kautz & Tingting Xiong & Daniela Klaus & Pascal Tomczyk & M, 2023. "Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43269-0
    DOI: 10.1038/s41467-023-43269-0
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    References listed on IDEAS

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