Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate

Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.4049/jimmunol.2001261
Journal or Publication Title: The Journal of Immunology
Volume: 207
Number: 9
Page Range: pp. 2278-2287
Date: 2021
Divisions: Lipid Metabolism and Neurochemistry
Depositing User: General Admin
Identification Number: 10.4049/jimmunol.2001261
ISSN: 0022-1767
Date Deposited: 17 Mar 2022 01:26

Systemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Exposure of C57BL/6 mice to doses of UV known to suppress systemic autoimmunity led to the accumulation of cells within the skin-draining lymph nodes and away from non-skin-draining lymph nodes. Transfer of CD45.1+ cells from nonirradiated donors into CD45.2+ UV-irradiated recipients resulted in preferential accumulation of donor naive T cells and a decrease in activated T cells within skin-draining lymph nodes. A single dose of immune-suppressive UV was all that was required to cause a redistribution of naive and central memory T cells from peripheral blood to the skin-draining lymph nodes. Specifically, CD69-independent increases in sphingosine-1-phosphate (S1P) receptor 1-negative naive and central memory T cells occurred in these lymph nodes. Mass spectrometry analysis showed UV-mediated activation of sphingosine kinase 1 activity, resulting in an increase in S1P levels within the lymph nodes. Topical application of a sphingosine kinase inhibitor on the skin prior to UV irradiation eliminated the UV-induced increase in lymph node S1P and T cell numbers. Thus, exposure to immunosuppressive UV disrupts T cell recirculation by manipulating the S1P pathway.

Tse, Benita C. Y.
Ireland, Rachael A.
Lee, Jun Yup
Marsh-Wakefield, Felix
Kok, Lai Fong
Don, Anthony S.
Byrne, Scott N.
Last Modified: 17 Mar 2022 01:26
URI: https://eprints.centenary.org.au/id/eprint/1197

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