Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Ostkamp, Patrick; Salmen, Anke; Pignolet, Béatrice; Görlich, Dennis; Andlauer, Till F M; Schulte-Mecklenbeck, Andreas; Gonzalez-Escamilla, Gabriel; Bucciarelli, Florence; Gennero, Isabelle; Breuer, Johanna; Antony, Gisela; Schneider-Hohendorf, Tilman; Mykicki, Nadine; Bayas, Antonios; Then Bergh, Florian; Bittner, Stefan; Hartung, Hans-Peter; Friese, Manuel A; Linker, Ralf A; Luessi, Felix; ... (2021). Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 118(1) National Academy of Sciences NAS 10.1073/pnas.2018457118

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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 (nNationMS = 946, nBIONAT = 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.

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