• Matthias Klein, Till-Julius Brühl, Valérie Staudt, Sebastian Reuter, Nadine Grebe, Bastian Gerlitzki, Markus Hoffmann, Toszka Bohn, Alexander Ulges, Natascha Stergiou, Jos de Graaf, Martin Löwer, Christian Taube, Marc Becker, Tobias Hain, Sarah Dietzen, Michael Stassen, Magdalena Huber, Michael Lohoff, Andrezza Campos Chagas, John Andersen, Jan Kotál, Helena Langhansová, Jan Kopecký, Hansjörg Schild, Michalis Kotsyfakis, Edgar Schmitt, and Tobias Bopp.
• Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany;
• J. Immunol. 2015 Jul 15; 195 (2): 621-31.

AbstractCoevolution of ticks and the vertebrate immune system has led to the development of immunosuppressive molecules that prevent immediate response of skin-resident immune cells to quickly fend off the parasite. In this article, we demonstrate that the tick-derived immunosuppressor sialostatin L restrains IL-9 production by mast cells, whereas degranulation and IL-6 expression are both unaffected. In addition, the expression of IL-1β and IRF4 is strongly reduced in the presence of sialostatin L. Correspondingly, IRF4- or IL-1R-deficient mast cells exhibit a strong impairment in IL-9 production, demonstrating the importance of IRF4 and IL-1 in the regulation of the Il9 locus in mast cells. Furthermore, IRF4 binds to the promoters of Il1b and Il9, suggesting that sialostatin L suppresses mast cell-derived IL-9 preferentially by inhibiting IRF4. In an experimental asthma model, mast cell-specific deficiency in IRF4 or administration of sialostatin L results in a strong reduction in asthma symptoms, demonstrating the immunosuppressive potency of tick-derived molecules. Copyright © 2015 by The American Association of Immunologists, Inc.

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