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

Journal of Investigative Dermatology

Clinical Summary

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What was studied

In a mouse model of UVB-induced immunosuppression to the chemical allergen 2,4-dinitrofluorobenzene, the investigators tested whether the UV photoproduct cis-urocanic acid reshapes skin bacteria and alters immune tolerance, using 16S sequencing, in vitro culture, LC-MS, and gnotobiotic-like mice. They also evaluated whether a topical urocanase inhibitor blocks bacterial metabolism of cis-urocanic acid.

Key findings

Acute UVB caused a transient restructuring of skin microbiota via cis-urocanic acid; Staphylococcus epidermidis and other HutU+ bacteria metabolized cis-urocanic acid, proliferated, and lowered its levels, which reduced UVR’s suppression of adaptive immunity and tolerance to 2,4-dinitrofluorobenzene. Topical inhibition of urocanase curtailed this metabolism and restored immunosuppression.

Study limitations

Preclinical mouse model under gnotobiotic-like conditions; no human data or clinical outcomes. Sample size and effect magnitudes were not reported in the abstract.

Clinical implications

This is mechanistic, preclinical evidence: the skin microbiome can blunt UV-induced immunosuppression, and blocking bacterial urocanase restored it in mice. Clinicians should view this as hypothesis-generating; human studies are needed before considering microbiome- or urocanase-targeted approaches to influence phototherapy responses.