6533b872fe1ef96bd12d42ef
RESEARCH PRODUCT
Tick Salivary Sialostatin L Represses the Initiation of Immune Responses by Targeting IRF4-Dependent Transcription in Murine Mast Cells
Natascha StergiouMarkus HoffmannJan KopeckýJan KopeckýToszka BohnMarc BeckerHansjörg SchildAlexander UlgesChristian TaubeMichael LohoffSebastian ReuterMichael StassenTobias BoppBastian GerlitzkiEdgar SchmittSarah DietzenMagdalena HuberMichalis KotsyfakisTobias HainMartin LöwerTill-julius BrühlJos De GraafHelena LanghansováHelena LanghansováMatthias KleinValérie StaudtNadine GrebeAndrezza C. ChagasJohn F. AndersenJan Kotálsubject
Transcription GeneticCell DegranulationInterleukin-1betaImmunologyBiologyArticleCell DegranulationHost-Parasite InteractionsMiceImmune systemImmunityAnimalsImmunology and AllergyInterleukin 9Mast CellsPromoter Regions GeneticMice KnockoutRegulation of gene expressionMice Inbred BALB CBinding SitesInterleukin-6Interleukin-9DegranulationReceptors Interleukin-1CystatinsAsthmaImmunity InnateMice Inbred C57BLGene Expression RegulationInterferon Regulatory FactorsImmunologySignal transductionImmunosuppressive AgentsProtein BindingSignal TransductionInterferon regulatory factorsdescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-07-15 |