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Tick Salivary Sialostatin L Represses the Initiation of Immune Responses by Targeting IRF4-Dependent Transcription in Murine Mast Cells

M. Klein, TJ. Brühl, V. Staudt, S. Reuter, N. Grebe, B. Gerlitzki, M. Hoffmann, T. Bohn, A. Ulges, N. Stergiou, J. de Graaf, M. Löwer, C. Taube, M. Becker, T. Hain, S. Dietzen, M. Stassen, M. Huber, M. Lohoff, A. Campos Chagas, J. Andersen, J....

. 2015 ; 195 (2) : 621-31. [pub] 20150615

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15031318

Coevolution 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.

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