UVB Light Attenuates the Systemic Immune Response in CNS Autoimmunity (P1.217)

OBJECTIVE: Investigation of mechanisms underlying the beneficial effects of immune regulatory processes induced locally in the skin by moderate UVB radiation leading to the attenuation of CNS autoimmunity. BACKGROUND: Environmental conditions play a critical role in the susceptibility and severity of autoimmune diseases. Multiple Sclerosis (MS), as well as most of the main autoimmune disorders, is characterized by a positive latitude gradient (the further away from the equator, the higher the disease incidence). DESIGN/METHODS: Effects of UVB light on autoimmune disease susceptibility and progression were analyzed in a murine model of CNS autoimmunity (EAE) utilizing different UV radiation protocols (pretreatment, prophylactic/therapeutic radiation and continuous treatment). Additionally, patients with relapsing-remitting MS were treated with narrowband UVB phototherapy five times weekly over a period of 6 weeks. Immunomodulatory effects of the clinical study were examined in skin biopsies, serum samples and in immune cells of the peripheral blood. RESULTS: Tregs, which are induced locally in the skin in response to UVB exposure, connect the cutaneous immune response to (CNS) autoimmunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg-inducing tolerogenic DCs, known to be critically involved in local immune responses of the skin, were further found to be necessary for induction of systemic immune regulation and tolerance by UVB radiation. Patients treated with UVB phototherapy showed elevated levels of vitamin D as well as an increase in induced Tregs and tolerogenic DCs together with the downregulation of the T-cell effector cytokine IL-21. CONCLUSIONS: UVB radiation of the skin can induce systemic immune regulation and tolerance via the induction of skin-derived tolerogenic DCs and Tregs. This has implications for the understanding or therapeutic modulation of environmental factors which influence autoimmune disorders such as MS. Disclosure: Dr. Breuer has nothing to disclose. Dr. Schwab has nothing to disclose. Dr. Schneider-Hohendorf has nothing to disclose. Dr. Marziniak has received personal compensation for activities with Merck Serono, Biogen Idec, Bayer Pharmaceuticals Inc., Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Marziniak has received research support from Merck Serono, Bayer Pharmaceuticals Inc., and Beiersdorf. Dr. Mohan has nothing to disclose. Dr. Bhatia has nothing to disclose. Dr. Gross has nothing to disclose. Dr. Weishaupt has nothing to disclose. Dr. Meuth has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., Bayer Schering, and Merck Serono. Dr. Loser has nothing to disclose. Dr. Wiendl has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Genzyme Corp., Merck Serono, Novartis, and Sanofi-Aventis Pharmaceutical Inc. Dr. Wiendl has received research support from Bayer Pharmaceuticals Corp., Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals Inc.