Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 2, Pages 621-631Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1401823
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Funding
- Deutsche Forschungsgemeinschaft [DFG BO 3306/1-1, SCHM 1014/7-1, SCHM 1014/5-1, SFB 1066, SFB TR22, GRK 1043]
- Behring-Rontgen-Stiftung
- Forschungszentrum Immunologie of the University Medical Center
- Czech Science Foundation Grant [P302/11/J029]
- Grant Agency of the Czech Republic [P502/12/2409]
- Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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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-1 beta 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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