Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity
Version of Record online: 13 MAY 2014
© 2014 American Neurological Association
Annals of Neurology
Volume 75, Issue 5, pages 739–758, May 2014
How to Cite
Breuer, J., Schwab, N., Schneider-Hohendorf, T., Marziniak, M., Mohan, H., Bhatia, U., Gross, C. C., Clausen, B. E., Weishaupt, C., Luger, T. A., Meuth, S. G., Loser, K. and Wiendl, H. (2014), Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity. Ann Neurol., 75: 739–758. doi: 10.1002/ana.24165
- Issue online: 10 JUN 2014
- Version of Record online: 13 MAY 2014
- Accepted manuscript online: 27 APR 2014 03:28AM EST
- Manuscript Accepted: 21 APR 2014
- Manuscript Revised: 17 APR 2014
- Manuscript Received: 9 JAN 2014
Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.
Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing–remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood.
Regulatory T cells (Tregs), which are induced locally in the skin-draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg-inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB-induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T-cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D.
Local UVB radiation of the skin influences systemic immune reactions and attenuates systemic autoimmunity via the induction of skin-derived tolerogenic DCs and Tregs. Our data could have implications for the understanding or therapeutic modulation of environmental factors that influence immune tolerance. Ann Neurol 2014;75:739–758