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Publications

Journal Article Ahead of print

PubMed: 40373957 DOI: 10.1016/j.jid.2025.03.035

Urocanase-Positive Skin-Resident Bacteria Metabolize cis-Urocanic Acid and in Turn Reduce the Immunosuppressive Properties of UVR.

J Invest Dermatol

Authors: VijayKumar Patra, Slave Trajanoski, Aaroh Joshi, Vanina Lenief, Chloe Goyet, Altan Cornu, Nicole Golob-Schwarzl, Meghana Somlapura, Amandine Mosnier, Maximilian Zarfl, Thomas Eichmann, Harald Köefeler, Mary Norval, Jean-Francois Nicolas, Peter Wolf, Marc Vocanson

Affiliations

  • Centre International de Recherche en Infectiologie (CIRI), INSERM, U1111, Univ Lyon, Université de Lyon 1, Ecole Normale Supérieure de Lyon, CNRS, UMR 5308, Lyon, France; Research Unit for Photodermatology, Medical University of Graz, Graz, Austria.
  • Computational Bioanalytics, Center for Medical Research, Medical University of Graz, Graz, Austria.
  • Research Unit for Photodermatology, Medical University of Graz, Graz, Austria.
  • Centre International de Recherche en Infectiologie (CIRI), INSERM, U1111, Univ Lyon, Université de Lyon 1, Ecole Normale Supérieure de Lyon, CNRS, UMR 5308, Lyon, France.
  • Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
  • Core Facility for Mass Spectrometry, Medical University of Graz, Graz, Austria.
  • Biomedical Sciences, University of Edinburgh Medical School, Edinburgh, United Kingdom.
  • Centre International de Recherche en Infectiologie (CIRI), INSERM, U1111, Univ Lyon, Université de Lyon 1, Ecole Normale Supérieure de Lyon, CNRS, UMR 5308, Lyon, France; Allergy and Clinical Immunology Department, Lyon Sud University Hospital, Lyon, France.
  • Research Unit for Photodermatology, Medical University of Graz, Graz, Austria.
  • Centre International de Recherche en Infectiologie (CIRI), INSERM, U1111, Univ Lyon, Université de Lyon 1, Ecole Normale Supérieure de Lyon, CNRS, UMR 5308, Lyon, France.

Abstract

The skin microbiome plays an important role in health and disease. We have recently shown that microbes living on the skin regulate the immunomodulatory properties of UVR, but the underlying mechanisms remain to be uncovered. Using a preclinical model of immunosuppression against the chemical allergen 2,4-dinitrofluorobenzene, 16S microbiome sequencing, in vitro cultures, high-performance liquid chromatography-mass spectrometry and the generation of gnotobiotic-like mice, we report that acute UVB radiation induces a transient and significant restructuring of bacterial communities on the skin through one of its major photoproducts, cis-urocanic acid. Certain bacteria, such as Staphylococcus epidermidis, use urocanase (HutU) to metabolize cis-urocanic acid to proliferate. This in turn affects the concentration of cis-urocanic acid on the skin, limiting its ability to suppress adaptive immune responses and induce tolerance to 2,4-dinitrofluorobenzene. Interestingly, addition of a topical urocanase inhibitor restricts the metabolism of cis-urocanic acid by HutU+ bacteria and restores immunosuppression. Overall, these results illustrate how, by harnessing a unique nutrient produced in response to UVR, urocanase-positive skin-resident bacteria can fine tune immune responses to environmental antigens. They should open new avenues to enhance the beneficial effects of phototherapy protocols and sun protection.

MeSH

Skin, Dinitrofluorobenzene, Urocanate Hydratase, Immunity, Urocanic Acid, Immunosuppression Therapy, Bacteria, Dermatology

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