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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Patra, V; Trajanoski, S; Joshi, A; Lenief, V; Goyet, C; Cornu, A; Golob-Schwarzl, N; Somlapura, M; Mosnier, A; Zarfl, M; Eichmann, T; Köefeler, H; Norval, M; Nicolas, JF; Wolf, P; Vocanson, M.
Urocanase-positive skin resident bacteria metabolize cis-urocanic acid and in turn reduce the immunosuppressive properties of UV radiation.
J Invest Dermatol. 2025; Doi: 10.1016/j.jid.2025.03.035
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Führende Autor*innen der Med Uni Graz
Patra Vijaykumar
Wolf Peter
Co-Autor*innen der Med Uni Graz
Eichmann Thomas
Golob-Schwarzl Nicole
Joshi Aaroh Anand
Köfeler Harald
Somlapura Meghana
Trajanoski Slave
Zarfl Maximilian
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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 ultraviolet (UV) radiation, but the underlying mechanisms remain to be uncovered. Using a pre-clinical model of immunosuppression against the chemical allergen 2,4-dinitrofluorobenzene (DNFB), 16S microbiome sequencing, in vitro cultures, HPLC-MS, as well as the generation of gnotobiotic-like mice, we report that acute UVB radiation induces a transient and significant restructuring of bacterial communities on the skin via one of its major photoproducts, cis-urocanic acid (cis-UCA). Certain bacteria, such as Staphylococcus epidermidis, use urocanase (HutU) to metabolize cis-UCA in order to proliferate. This in turn affects the concentration of cis-UCA, limiting its ability to suppress adaptive immune responses and induce tolerance to DNFB. Interestingly, addition of a topical urocanase inhibitor restricts the metabolism of cis-UCA by HutU+ bacteria and restores immunosuppression. Overall, these results illustrate how, by harnessing a unique nutrient produced in response to solar UV radiation, 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, as well as sun protection.

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