Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Neurology, University of Münster, Münster.
Johanna
J
Breuer
Nicholas
N
Schwab
Tilman
T
Schneider-Hohendorf
Martin
M
Marziniak
Hema
H
Mohan
Urvashi
U
Bhatia
Catharina C
CC
Gross
Björn E
BE
Clausen
Carsten
C
Weishaupt
Thomas A
TA
Luger
Sven G
SG
Meuth
Karin
K
Loser
Heinz
H
Wiendl
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy / Q000379:methods; D055815:Young Adult