UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo

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Abstract

Objectives: Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR-induced inflammation are well-documented, the mediation of its resolution and longer-term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation.

Methods: To investigate the self-resolving events of UVR inflammation in vivo, human skin was exposed to a single pro-inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post-UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry.

Results: We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR-induced inflammation in humans involves a post-resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T-cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post-UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure.

Conclusion: We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T-cell subpopulations are recruited to UVR-inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T-cell subpopulations and also the persistent alteration of the lipid microenvironment post-UVR.

Bibliographical metadata

Original languageEnglish
Pages (from-to)e01104
JournalClinical & translational immunology
Volume9
Issue number4
DOIs
Publication statusPublished - 2 Apr 2020