Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
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Ostkamp, Patrick | Salmen, Anke | Pignolet, Béatrice | Görlich, Dennis | Andlauer, Till | 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 | Linker, Ralf | Luessi, Felix | Lehmann-Horn, Klaus | Mühlau, Mark | Paul, Friedemann | Stangel, Martin | Tackenberg, Björn | Tumani, Hayrettin | Warnke, Clemens | Weber, Frank | Wildemann, Brigitte | Zettl, Uwe | Ziemann, Ulf | Müller-Myhsok, Bertram | Kümpfel, Tania | Klotz, Luisa | Meuth, Sven | Zipp, Frauke | Hemmer, Bernhard | Hohlfeld, Reinhard | Brassat, David | Gold, Ralf | Gross, Catharina | Lukas, Carsten | Groppa, Sergiu | Loser, Karin | Wiendl, Heinz | Schwab, Nicholas | Rothacher, Susanne | Starke, Stephanie | Bellmann-Strobl, Judith | Behrens, Janina | Dörr, Jan-Markus | Giess, Rene | Kuchling, Joseph | Rasche, Ludwig | Chan, Andrew | Ellrichmann, Gisa | Fisse, Anna Lena | Gahlen, Anna | Grüter, Thomas | Haghikia, Aiden | Hoepner, Robert | Koc, Ümmügülsün | Motte, Jeremias | Pitarokoili, Kalliopi | Schneider, Ruth | Schöllhammer, Joanna | Schroeder, Christoph | Ambrosius, Björn | Demir, Seray | Dehmel, Thomas | Ingenhoven, Kathleen | Lee, De-Hyung | Lämmer, Alexandra | Sauer, Eva | Heesen, Christoph | Stellmann, Jan-Patrick | Boenig, Lena | Gingele, Stefan | Hümmert, Martin | Schwenkenbecher, Philipp | Skripuletz, Thomas | Suehs, Wolfram | Korporal-Kuhnke, Mirjam | Osswald, Hanna | Schwarz, Alexander | Viehöver, Andrea | Limmroth, Volker | Gerbershagen, Kathrin | Bergh, Florian Then | Ettrich, Barbara | Gray, Steffi | Haars, Sarah | Orthgiess, Johannes | Schwanitz, Nicole | Stoppe, Muriel | Unterlauft, Astrid | Paryjas, Sandra | Fleischer, Vinzenz | Lüssi, Felix | Piepgras, Johannes | Uphaus, Timo | Pütz, Michael | Eienbröker, Christian | Seipelt, Maria | Havla, Joachim | Meinl, Ingrid | Pellkofer, Hannah | Schuh, Elisabeth | Aly, Lilian | Berthele, Achim | Pongratz, Viola | Brinkhoff, Kirsten | Buck, Dorothea | Gasperi, Christiane | Hermisson, Mirjam | Hoshi, Muna-Miriam | Kaminski, Miriam | Klein, Ana | Knier, Benjamin | Kowarik, Markus | Kronsbein, Helena | Horn, Klaus Lehmann | Mitsdörffer, Meike | Pernpeintner, Verena | Rothhammer, Veit | Schweikert, Andrea | Selter, Rebecca | Zimmer, Claus | Kirschke, Jan | Staufer, Heike | Knop, Matthias | Nischwitz, Sandra | Sämann, Philipp | Meyer zu Hörste, Gerd | Krämer, Julia | Schünemann, Lena | Pfeuffer, Steffen | Ruck, Tobias | Belgriri, Selma | Buchheister, Alexander | Bünger, Nora | Göbel, Kerstin | Kirstein, Lucienne | Melzer, Nico | Simon, Ole | Echterhoff, Antje | Winkelmann, Alexander | Abdelhak, Ahmed | Krumbholz, Markus | Paech, Margarete | Ruschil, Christoph | Stefanou, Maria-Ioanna | Tünnerhoff, Johannes | Zeltner, Lena | Sheikh, Hajera | Fangerau, Tanja | Lauda, Florian | Rau, Daniela | Taranu, Daniela | Huss, André | Scandella, Lise | Lebrun-Frenay, Christine | Debouverie, Marc | Pittion-Vouyovitch, Sophie | Brochet, Bruno | Ruet, Aurelie | Defer, Gilles | Derache, Nathalie | de Sèze, Jérôme | Laplaud, David | Wiertlewski, Sandrine | Casez, Oliver | Clavelou, Pierre | Labauge, Pierre | Pelletier, Jean | Rico, Audrey | Vukusic, Sandra | Outteryck, Olivier | Ouallet, Jean-Christophe | Hautecoeur, Patrick | Tourbah, Ayman | Castelnovo, Giovanni | Berger, Eric | Zéphir, Hélène | Cabre, Philippe | Camu, William | Thouvenot, Eric | Moreau, Thibault | Fromont, Agnès | Papeix, Caroline | Lubetzki, Catherine | Vermersch, Patrick | Cohen, Mikael | Rumbach, Lucien
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CCSD ; National Academy of Sciences -
International audience.
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 (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-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.
