title: Ixodes ricinus salivary serpin IRS-2 affects Th17 differentiation via inhibition of the interleukin-6/STAT-3 signaling pathway.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jana
authors.initials: J
authors.lastname: Páleníková
authors.affiliation: 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.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Lieskovská
authors.affiliation: 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.
authors.forename: Helena
authors.initials: H
authors.lastname: Langhansová
authors.affiliation: Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branišovská, České Budějovice, Czech Republic.
authors.forename: Michalis
authors.initials: M
authors.lastname: Kotsyfakis
authors.affiliation: Faculty of Science, University of South Bohemia, Branišovská, České Budějovice, Czech Republic Department of Clinical Pathobiochemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Chmelař
authors.affiliation: 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 jan@paru.cas.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecký
mesh_terms: D000818:Animals; D001898:Borrelia / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D018884:Ixodes; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015843:Serpins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects* / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D015843:Serpins; D000093242:Interleukin-6 Inhibitors; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse