UV radiation recruits CD4+GATA3+ and CD8+GATA3+ Tcells while altering the lipid microenvironment following inflammatory resolution in human skin in vivoCitation formats

TY - JOUR

T1 - UV radiation recruits CD4+GATA3+ and CD8+GATA3+ Tcells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo

AU - Hawkshaw, Nathan

AU - Pilkington, Suzanne

AU - Murphy, Sharon

AU - Al-Gazaq, Norah

AU - Farrar, Mark

AU - Watson, Rachel

AU - Nicolaou, Anna

AU - Rhodes, Lesley

PY - 2020/4/2

Y1 - 2020/4/2

N2 - 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 immunohistochemisty 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+ T40 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.

AB - 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 immunohistochemisty 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+ T40 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.

KW - Immunosuppression

KW - Immunotherapy

KW - Immunology

KW - CD8-positive T cells

KW - T cells

KW - Lymphocytes

KW - Immunology, CD4-positive T cells

KW - Immunology, Translational immunology

KW - Immunology, inflammation

KW - Innate immune cells

KW - Immunology, lipidomics

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114692/

M3 - Article

VL - 9

JO - Clinical & translational immunology

JF - Clinical & translational immunology

SN - 2050-0068

IS - 4

M1 - e01104

ER -