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Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

2020; National Academy of Sciences; Volume: 118; Issue: 1 Linguagem: Inglês

10.1073/pnas.2018457118

1091-6490

Patrick Ostkamp, Anke Salmen, Béatrice Pignolet, Dennis Görlich, Till F. M. Andlauer, Andreas Schulte‐Mecklenbeck, Gabriel González‐Escamilla, Florence Bucciarelli, Isabelle Gennero, Johanna Breuer, Gisela Antony, Tilman Schneider‐Hohendorf, Nadine Mykicki, Antonios Bayas, Florian Then Bergh, Stefan Bittner, Hans‐Peter Hartung, Manuel A. Friese, Ralf A. Linker, Felix Luessi, Klaus Lehmann‐Horn, Mark Mühlau, Friedemann Paul, Martin Stangel, Björn Tackenberg, Hayrettin Tumani, Clemens Warnke, Frank Weber, Brigitte Wildemann, Uwe K. Zettl, Ulf Ziemann, Bertram Müller‐Myhsok, Tania Kümpfel, Luisa Klotz, Sven G. Meuth, Frauke Zipp, Bernhard Hemmer, Reinhard Hohlfeld, David Brassat, Ralf Gold, Catharina C. Groß, Carsten Lukas, Sergiu Groppa, Karin Loser, Heinz Wiendl, Nicholas Schwab, Antonios Bayas, Susanne Rothacher, Stephanie Starke, Friedemann Paul, Judith Bellmann‐Strobl, Janina Behrens, Jan-Markus Dörr, René M. Gieß, Joseph Kuchling, Ludwig Rasche, Ralf Gold, Andrew T. Chan, Gisa Ellrichmann, Anna Lena Fisse, Anna Gahlen, Thomas Grüter, Aiden Haghikia, Robert Hoepner, U.-V. Koc, Carsten Lukas, Jeremias Motte, Kalliopi Pitarokoili, Anke Salmen, Ruth Schneider, Joanna Schöllhammer, Christoph Schroeder, Björn Ambrosius, Seray Demir, Clemens Warnke, Thomas Dehmel, Kathleen Ingenhoven, Ralf A. Linker, De-Hyung Lee, Alexandra Lämmer, Eva Sauer, Christoph Heesen, Jan‐Patrick Stellmann, Martin Stangel, Lena Boenig, Stefan Gingele, Martin W. Hümmert, Philipp Schwenkenbecher, Thomas Skripuletz, Wolfram Suehs, Brigitte Wildemann, Mirjam Korporal‐Kuhnke, Hanna Oßwald, Alexander Schwarz, Andrea Viehöver, Volker Limmroth, Kathrin Gerbershagen, Florian Then Bergh, Barbara Ettrich, Steffi Gray, Sarah Haars, Johannes Orthgieß, Nicole Schwanitz, Muriel Stoppe, Astrid Unterlauft, Sandra Paryjas, Stefan Bittner, Vinzenz Fleischer, Sergiu Groppa, Felix Lüssi, Johannes Piepgras, Timo Uphaus, Björn Tackenberg, Michael Pütz, Christian Eienbröker, Maria Seipelt, Reinhard Hohlfeld, Tania Kümpfel, Joachim Havla, Ingrid Meinl, Hannah Pellkofer, Elisabeth Schuh, Bernhard Hemmer, Lilian Aly, Achim Berthele, Viola Pongratz, Kirsten Brinkhoff, Dorothea Buck, Christiane Gasperi, Mirjam Hermisson, Muna‐Miriam Hoshi, Miriam Kaminski, Ana Paula Klein, Benjamin Knier, Markus Kowarik, Helena Kronsbein, K Horn, Meike Mitsdörffer, Verena Pernpeintner, Veit Rothhammer, Andrea Schweikert, Rebecca Selter, Mark Mühlau, Claus Zimmer, Jan S. Kirschke, Frank Weber, Heike Staufer, Matthias Knop, Sandra Nischwitz, Philipp Sämann, Heinz Wiendl, Sven G. Meuth, Luisa Klotz, Gerd Meyer zu Hörste, Julia Krämer, Lena Schünemann, Catharina C. Groß, Steffen Pfeuffer, Tobias Ruck, Selma Belgriri, Alexander Buchheister, Nora Bünger, Kerstin Göbel, Lucienne Kirstein, Nico Melzer, Ole J. Simon, Antje K. C. Echterhoff, Uwe K. Zettl, Alexander Winkelmann, Ulf Ziemann, Ahmed Abdelhak, Markus Kowarik, Markus Krumbholz, Margarete Paech, Christoph Ruschil, Maria‐Ioanna Stefanou, Johannes Tünnerhoff, Lena Zeltner, Hajera Sheikh, Hayrettin Tumani, Tanja Fangerau, Florian Lauda, Daniela Rau, Daniela Taranu, André Huss, David Brassat, Béatrice Pignolet, Florence Bucciarelli, Lise Scandella, Christine Lebrun-Frenay, Marc Debouverie, S. Pittion‐Vouyovitch, Bruno Brochet, Aurélie Ruet, Gilles Defer, Nathalie Derache, de Sèze, David Laplaud, Sandrine Wiertlewski, O. Casez, Pierre Clavelou, Pierre Labauge, Jean Pelletier, Audrey Rico, Sandra Vukusic, Olivier Outteryck, Jean-Claude, Jean‐Christophe Ouallet, Patrick Hautecœur, Ayman Tourbah, Giovanni Castelnovo, Eric Berger, Hélène Zéphir, Philippe Cabre, William Camu, Éric Thouvenot, Thibault Moreau, Agnès Fromont, Caroline Papeix, Catherine Lubetzki, Patrick Vermersch, Mikaël Cohen, L. Rumbach,

Reproductive System and Pregnancy

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.