@article{f607b12f24424a87ae5a57c3d7f259a4,
title = "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",
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.",
keywords = "MAIT cells, MR1, atopic dermatitis, phototherapy",
author = "Karmella Naidoo and Katherine Woods and Christophe Pellefigues and Alissa Cait and David O'Sullivan and Katie Gell and Marshall, {Andrew J.} and Anderson, {Regan J.} and Yanyan Li and Alfonso Schmidt and Kef Prasit and Mayer, {Johannes U.} and Aurelie Gestin and Hermans, {Ian F.} and Gavin Painter and Jacobsen, {Elizabeth A.} and Olivier Gasser",
note = "Funding Information: This work was supported by the New Zealand Health Research Council Independent Research Organization Fund (14/1003), the High-Value Nutrition National Science Challenge, New Zealand, the New Zealand Ministry of Business Innovation and Employment (RTVU1603), Dairy Goat Co-operative Limited, New Zealand and the New Zealand Ministry for Primary Industries as part of the Caprine Innovations NZ (CAPRINZ) Sustainable Food & Fibre Futures program. We are grateful to the staff of the Hugh Green Cytometry Core and Biomedical Research Unit at the Malaghan Institute of Medical Research for expert support with flow cytometry and animal husbandry and all colleagues at the Malaghan Institute for insightful discussion and advice. We thank the NIH Tetramer Facility for providing the 5-OP-RU- and 6-FP-loaded MR1 tetramers. The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne, Australia. Dr. Naidoo is listed as an inventor on a pending patent protecting the use of MR1 ligands in the context of inflammatory skin diseases. Dr Woods, Dr. Pellefigues, Dr. Cait, Dr. O'Sullivan, Ms. Gell, Ms. Li, A.J. Schmidt, Dr. Prasit, Dr. Mayer, Dr. Gestin, and Dr. Jacobsen have nothing to disclose. Dr. Marshall and Dr. Anderson report grants from Ministry of Business Innovation and Employment during the conduct of the study. IH declares no conflicts of interest. Dr. Painter reports grants from NZ Ministry of Business Innovation and Employment, grants from the NZ Health Research Council, during the conduct of the study. Dr. Gasser is listed as an inventor on a pending patent protecting the use of MR1 ligands in the context of inflammatory skin diseases. Funding Information: This work was supported by the New Zealand Health Research Council Independent Research Organization Fund (14/1003), the High‐Value Nutrition National Science Challenge, New Zealand, the New Zealand Ministry of Business Innovation and Employment (RTVU1603), Dairy Goat Co‐operative Limited, New Zealand and the New Zealand Ministry for Primary Industries as part of the Caprine Innovations NZ (CAPRINZ) Sustainable Food & Fibre Futures program. We are grateful to the staff of the Hugh Green Cytometry Core and Biomedical Research Unit at the Malaghan Institute of Medical Research for expert support with flow cytometry and animal husbandry and all colleagues at the Malaghan Institute for insightful discussion and advice. We thank the NIH Tetramer Facility for providing the 5‐OP‐RU‐ and 6‐FP‐loaded MR1 tetramers. The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie, and the material was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne, Australia. Dr. Naidoo is listed as an inventor on a pending patent protecting the use of MR1 ligands in the context of inflammatory skin diseases. Dr Woods, Dr. Pellefigues, Dr. Cait, Dr. O'Sullivan, Ms. Gell, Ms. Li, A.J. Schmidt, Dr. Prasit, Dr. Mayer, Dr. Gestin, and Dr. Jacobsen have nothing to disclose. Dr. Marshall and Dr. Anderson report grants from Ministry of Business Innovation and Employment during the conduct of the study. IH declares no conflicts of interest. Dr. Painter reports grants from NZ Ministry of Business Innovation and Employment, grants from the NZ Health Research Council, during the conduct of the study. Dr. Gasser is listed as an inventor on a pending patent protecting the use of MR1 ligands in the context of inflammatory skin diseases. Publisher Copyright: {\textcopyright} 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",
year = "2021",
month = oct,
doi = "10.1111/all.14994",
language = "English (US)",
volume = "76",
pages = "3155--3170",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "10",
}