Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

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 (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.

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood

“…Furthermore, the in vitro functional responses of memory B cell subsets for production of the pro-inflammatory cytokine, tumour necrosis factor, was reduced at the end of the phototherapy ( 35 ). These results suggest that NB-UVB may have potential to reduce the pathology of B-cell driven immune conditions by reducing inflammatory cell-cell-communication and inflammatory cytokine production, possibly involving the induction of type I IFN and its associated pathways ( 36 ).…”

Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis

“…Another study found that the correlation of ultraviolet B exposure with reduced MS prevalence is more pronounced in females (r = −0.76) compared to males (r = −0.46) [140]. Beneficial effects of sun exposure were also reported for established MS, with higher latitude being associated with worse MS severity scores (MSSS) (β = 0.092 per degree in latitude), increased risk of active MS lesions (RR = 1.08) and disability accumulation over time (∆EDSS) (β = 0.067) [141].…”

Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody‐associated disease

“…86 Vitamin D and UV exposure Low vitamin D levels, insufficient UV exposure and higher latitudes have each been linked to an increased risk of developing MS. 87 In a recent study of two independent multicentre cohorts, lower disease severity was seen in MS patients with higher vitamin D levels. 88 Although UV exposure is correlated with the maintenance of sufficient levels of vitamin D, the role of sun exposure in the development of MS may be vitamin D-independent. 89 For instance, while whole-body UV irradiation of mice prevents the development of EAE, 90 UV-induced suppression of EAE was still observed in mice lacking the vitamin D receptor.…”

“…Low vitamin D levels, insufficient UV exposure and higher latitudes have each been linked to an increased risk of developing MS 87 . In a recent study of two independent multicentre cohorts, lower disease severity was seen in MS patients with higher vitamin D levels 88 . Although UV exposure is correlated with the maintenance of sufficient levels of vitamin D, the role of sun exposure in the development of MS may be vitamin D‐independent 89 .…”