MR1-dependent immune surveillance of the skin contributes to pathogenesis and is a photobiological target of UV light therapy in a mouse model of atopic dermatitis

Karmella Naidoo, Katherine Woods, Christophe Pellefigues, Alissa Cait, David O'Sullivan, Katie Gell, Andrew J. Marshall, Regan J. Anderson, Yanyan Li, Alfonso Schmidt, Kef Prasit, Johannes U. Mayer, Aurelie Gestin, Ian F. Hermans, Gavin Painter, Elizabeth A. Jacobsen, Olivier Gasser

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mucosal-associated invariant T (MAIT) cells are unconventional T cells which recognize microbial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although MAIT cells have been shown to reside in human and murine skin, their contribution to atopic dermatitis (AD), an inflammatory skin disease associated with barrier dysfunction and microbial translocation, has not yet been determined. Methods: Genetic deletion of MR1 and topical treatment with inhibitory MR1 ligands, which result in the absence and functional inhibition of MAIT cells, respectively, were used to investigate the role of MR1-dependent immune surveillance in a MC903-driven murine model of AD. Results: The absence or inhibition of MR1 arrested AD disease progression through the blockade of both eosinophil activation and recruitment of IL-4- and IL-13-producing cells. In addition, the therapeutic efficacy of phototherapy against MC903-driven AD could be increased with prior application of folate, which photodegrades into the inhibitory MR1 ligand 6-formylpterin. Conclusion: We identified MAIT cells as sentinels and mediators of cutaneous type 2 immunity. Their pathogenic activity can be inhibited by topical application or endogenous generation, via phototherapy, of inhibitory MR1 ligands.

Original languageEnglish (US)
Pages (from-to)3155-3170
Number of pages16
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume76
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • atopic dermatitis
  • MAIT cells
  • MR1
  • phototherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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