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Keratinocyte-derived microvesicle particles mediate Ultraviolet B radiation induced systemic immunosuppression
Langni Liu, … , R. Michael Johnson, Jeffrey B. Travers
Langni Liu, … , R. Michael Johnson, Jeffrey B. Travers
Published April 8, 2021
Citation Information: J Clin Invest. 2021. https://doi.org/10.1172/JCI144963.
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Research In-Press Preview Dermatology Immunology

Keratinocyte-derived microvesicle particles mediate Ultraviolet B radiation induced systemic immunosuppression

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Abstract

A complete carcinogen, Ultraviolet B radiation (290-320 nm; UVB), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator Platelet-activating factor. A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF Receptor (PAFR) activation in keratinocytes induce large amounts of microvesicle particle (extracellular vesicles 100-1000nm; MVP) release. MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVP) are dependent upon the keratinocyte PAFR. The present studies used both pharmacologic and genetic approaches in cells and mice to determine that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVP leaving the keratinocyte can be found systemically in mice and in human subjects following UVB. Moreover, UVB-MVP contain bioactive contents including PAFR agonists which allow them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression.

Authors

Langni Liu, Azeezat A. Awoyemi, Katherine E. Fahy, Pariksha Thapa, Christina Borchers, Benita Y. Wu, Cameron L. McGlone, Benjamin Schmeusser, Zafer Sattouf, Craig A. Rohan, Amy R. Williams, Elizabeth E. Cates, Christina Knisely, Lisa E. Kelly, Ji C. Bihl, David R. Cool, Ravi P. Sahu, Jinju Wang, Yanfang Chen, Christine M. Rapp, Michael G. Kemp, R. Michael Johnson, Jeffrey B. Travers

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Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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