Th17 cells constitute a subset of CD4(+) T lymphocytes that play a crucial role in protection against extracellular bacteria and fungi. They are also associated with tissue injury in autoimmune and inflammatory diseases. Here, we report that serpin from the tick Ixodes ricinus, IRS-2, inhibits Th17 differentiation by impairment of the interleukin-6 (IL-6)/STAT-3 signaling pathway. Following activation, mature dendritic cells produce an array of cytokines, including the pleiotropic cytokine IL-6, which triggers the IL-6 signaling pathway. The major transcription factor activated by IL-6 is STAT-3. We show that IRS-2 selectively inhibits production of IL-6 in dendritic cells stimulated with Borrelia spirochetes, which leads to attenuated STAT-3 phosphorylation and finally to impaired Th17 differentiation. The results presented extend the knowledge about the effect of tick salivary serpins on innate immunity cells and their function in driving adaptive immune responses.

Faculty of Science University of South Bohemia Branišovská České Budějovice Czech Republic Department of Clinical Pathobiochemistry Technische Universität Dresden Dresden Germany

Faculty of Science University of South Bohemia Branišovská České Budějovice Czech Republic Institute of Parasitology Biology Centre of the Academy of Sciences of the Czech Republic Branišovská České Budějovice Czech Republic

Institute of Parasitology Biology Centre of the Academy of Sciences of the Czech Republic Branišovská České Budějovice Czech Republic

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