Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Proc Natl Acad Sci U S A. 2021 Jan 5;118(1):e2018457118. doi: 10.1073/pnas.2018457118.


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.

Keywords: latitude; melanocortin 1 receptor; multiple sclerosis; sunlight; vitamin D.

Publication types

  • Multicenter Study

MeSH terms

  • B-Lymphocytes / radiation effects
  • Cohort Studies
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Monocytes / radiation effects*
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / radiotherapy
  • Phenotype
  • Phototherapy
  • Receptor, Melanocortin, Type 1 / genetics*
  • Recurrence
  • Severity of Illness Index
  • Sunlight
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / radiation effects
  • Transcriptome / genetics
  • Transcriptome / radiation effects*
  • Vitamin D / blood*


  • MC1R protein, human
  • Receptor, Melanocortin, Type 1
  • Vitamin D
  • Interferon-beta