Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
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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; Lehmann-Horn, Klaus; Mühlau, Mark; Paul, Friedemann; Stangel, Martin; Tackenberg, Björn; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Müller-Myhsok, Bertram; Kümpfel, Tania; Klotz, Luisa; Meuth, Sven G; Zipp, Frauke; Hemmer, Bernhard; Hohlfeld, Reinhard; Brassat, David; Gold, Ralf; Gross, Catharina C; Lukas, Carsten; Groppa, Sergiu; Loser, Karin; Wiendl, Heinz; Schwab, Nicholas; German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network.
in: P NATL ACAD SCI USA, Jahrgang 118, Nr. 1, 05.01.2021, S. e2018457118.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
AU - Ostkamp, Patrick
AU - Salmen, Anke
AU - Pignolet, Béatrice
AU - Görlich, Dennis
AU - Andlauer, Till F M
AU - Schulte-Mecklenbeck, Andreas
AU - Gonzalez-Escamilla, Gabriel
AU - Bucciarelli, Florence
AU - Gennero, Isabelle
AU - Breuer, Johanna
AU - Antony, Gisela
AU - Schneider-Hohendorf, Tilman
AU - Mykicki, Nadine
AU - Bayas, Antonios
AU - Then Bergh, Florian
AU - Bittner, Stefan
AU - Hartung, Hans-Peter
AU - Friese, Manuel A
AU - Linker, Ralf A
AU - Luessi, Felix
AU - Lehmann-Horn, Klaus
AU - Mühlau, Mark
AU - Paul, Friedemann
AU - Stangel, Martin
AU - Tackenberg, Björn
AU - Tumani, Hayrettin
AU - Warnke, Clemens
AU - Weber, Frank
AU - Wildemann, Brigitte
AU - Zettl, Uwe K
AU - Ziemann, Ulf
AU - Müller-Myhsok, Bertram
AU - Kümpfel, Tania
AU - Klotz, Luisa
AU - Meuth, Sven G
AU - Zipp, Frauke
AU - Hemmer, Bernhard
AU - Hohlfeld, Reinhard
AU - Brassat, David
AU - Gold, Ralf
AU - Gross, Catharina C
AU - Lukas, Carsten
AU - Groppa, Sergiu
AU - Loser, Karin
AU - Wiendl, Heinz
AU - Schwab, Nicholas
AU - German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network
N1 - Copyright © 2021 the Author(s). Published by PNAS.
PY - 2021/1/5
Y1 - 2021/1/5
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.2018457118
DO - 10.1073/pnas.2018457118
M3 - SCORING: Journal article
C2 - 33376202
VL - 118
SP - e2018457118
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 1
ER -