1. Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate
- Author
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Anthony S. Don, Jun Yup Lee, Rachael A. Ireland, Scott N. Byrne, Lai Fong Kok, Benita C. Y. Tse, and Felix Marsh-Wakefield
- Subjects
Multiple Sclerosis ,Ultraviolet Rays ,T cell ,Immunology ,Sphingosine kinase ,Lymphocyte Activation ,Mice ,chemistry.chemical_compound ,Immune system ,Sphingosine ,medicine ,Animals ,Humans ,Immunology and Allergy ,Sphingosine-1-phosphate ,Receptor ,Sphingosine-1-Phosphate Receptors ,Lymph node ,Cells, Cultured ,Skin ,Immunosuppression Therapy ,biology ,Chemistry ,Mice, Inbred C57BL ,Phosphotransferases (Alcohol Group Acceptor) ,medicine.anatomical_structure ,Sphingosine kinase 1 ,Blood Circulation ,Cancer research ,biology.protein ,Ultraviolet Therapy ,Lymph Nodes ,Lymph ,Lysophospholipids ,Immunologic Memory ,Signal Transduction - Abstract
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.
- Published
- 2021