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Item Type: | Article |
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Title: | Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity |
Creators Name: | Ostkamp, P., Salmen, A., Pignolet, B., Görlich, D., Andlauer, T.F.M., Schulte-Mecklenbeck, A., Gonzalez-Escamilla, G., Bucciarelli, F., Gennero, I., Breuer, J., Antony, G., Schneider-Hohendorf, T., Mykicki, N., Bayas, A., Then Bergh, F., Bittner, S., Hartung, H.P., Friese, M.A., Linker, R.A., Luessi, F., Lehmann-Horn, K., Mühlau, M., Paul, F., Stangel, M., Tackenberg, B., Tumani, H., Warnke, C., Weber, F., Wildemann, B., Zettl, U.K., Ziemann, U., Müller-Myhsok, B., Kümpfel, T., Klotz, L., Meuth, S.G., Zipp, F., Hemmer, B., Hohlfeld, R., Brassat, D., Gold, R., Gross, C.C., Lukas, C., Groppa, S., Loser, K., Wiendl, H. and Schwab, N. |
Abstract: | Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (n(NationMS) = 946, n(BIONAT) = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of MC1R:rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS. |
Keywords: | Sunlight, Multiple Sclerosis, Vitamin D, Latitude, Melanocortin 1 Receptor |
Source: | Proceedings of the National Academy of Sciences of the United States of America |
ISSN: | 0027-8424 |
Publisher: | National Academy of Sciences |
Volume: | 118 |
Number: | 1 |
Page Range: | e2018457118 |
Date: | 5 January 2021 |
Additional Information: | Erratum in: PNAS 118(29): e2110306118 |
Official Publication: | https://doi.org/10.1073/pnas.2018457118 |
PubMed: | View item in PubMed |
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