4.8 Article

Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2018457118

Keywords

sunlight; multiple sclerosis; vitamin D; latitude; melanocortin 1 receptor

Funding

  1. German Ministry for Education and Research (BMBF)
  2. Deutsche Forschungsgemeinschaft (DFG)
  3. Interdisciplinary Center for Clinical Studies (IZKF) Muenster
  4. Biogen
  5. Merck
  6. Novartis
  7. BMBF [01Gl1603A]
  8. DFG [GR3946/3-1, SFB Transregio 128 A09]
  9. Landesforschungsforderung Hamburg
  10. Gemeinnutzige HertieStiftung
  11. Else Kroner-Fresenius-Stiftung
  12. Else Kroner Fresenius Foundation
  13. German Academic Exchange Service
  14. Hertie Foundation
  15. IZKF Muenster
  16. German Foundation Neurology and Almirall
  17. Amicus Therapeutics Germany
  18. Diamed
  19. Fresenius Medical Care
  20. Genzyme
  21. Merck Serono
  22. ONO Pharma
  23. Roche
  24. Teva
  25. GenzymeSanofi
  26. Bayer Schering AG
  27. Chugai Pharma
  28. European Research Council
  29. Bristol Myers Squibb
  30. Janssen Pharmaceuticals NV
  31. Servier
  32. Biogen Idec
  33. Pharmaceutical Management Science Association
  34. Octapharma
  35. Celgene
  36. Sanofi Aventis
  37. European Union
  38. IZKF
  39. Innovative Medizinische Forschung

Ask authors/readers for more resources

The study found that high serum vitamin D levels were associated with reduced MS severity, lower relapse risk, and slower disability accumulation, while low latitude was linked to higher vitamin D levels, lower MS severity, fewer lesions, and less disability accumulation. Sun exposure may have beneficial effects on established MS, but could potentially be harmful for photosensitive individuals. Additionally, UV-mediated immune-modulation in MS may involve direct induction of type I interferons.
Multiple sclerosis (MS) disease risk is associated with reduced sunexposure. 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-beta-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 benefidal 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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