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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\u2013skin-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\u2013negative 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2001261","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T17:10:14Z","timestamp":1632503414000},"page":"2278-2287","source":"Crossref","is-referenced-by-count":9,"title":["Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-8056","authenticated-orcid":false,"given":"Benita C Y","family":"Tse","sequence":"first","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-6149","authenticated-orcid":false,"given":"Rachael A","family":"Ireland","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Westmead Institute for Medical Research, Centre for Immunology and Allergy Research , Westmead, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3983-4024","authenticated-orcid":false,"given":"Jun Yup","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-7628","authenticated-orcid":false,"given":"Felix","family":"Marsh-Wakefield","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-9159","authenticated-orcid":false,"given":"Lai Fong","family":"Kok","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1655-1184","authenticated-orcid":false,"given":"Anthony S","family":"Don","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Centenary Institute, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-1710","authenticated-orcid":false,"given":"Scott N","family":"Byrne","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Westmead Institute for Medical Research, Centre for Immunology and Allergy Research , Westmead, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"2025022610322117100_r1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1073\/pnas.74.4.1688","article-title":"Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis","volume":"74","author":"Fisher","year":"1977","journal-title":"Proc. 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