Páleníková Jana, Lieskovská Jaroslava, Langhansová Helena, Kotsyfakis Michalis, Chmelař Jindřich, Kopecký Jan
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.
Infect Immun. 2015 May;83(5):1949-56. doi: 10.1128/IAI.03065-14. Epub 2015 Feb 23.
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.
辅助性T细胞17（Th17细胞）是CD4(+) T淋巴细胞的一个亚群，在抵御细胞外细菌和真菌方面发挥着关键作用。它们也与自身免疫性疾病和炎症性疾病中的组织损伤有关。在此，我们报告蓖麻蜱（Ixodes ricinus）的丝氨酸蛋白酶抑制剂IRS-2通过损害白细胞介素-6（IL-6）/信号转导和转录激活因子3（STAT-3）信号通路来抑制Th17细胞分化。激活后，成熟的树突状细胞会产生一系列细胞因子，包括多效性细胞因子IL-6，其可触发IL-6信号通路。由IL-6激活的主要转录因子是STAT-3。我们发现，IRS-2可选择性抑制受伯氏疏螺旋体刺激的树突状细胞中IL-6的产生，这会导致STAT-3磷酸化减弱，最终导致Th17细胞分化受损。所呈现的结果扩展了关于蜱唾液丝氨酸蛋白酶抑制剂对固有免疫细胞的影响及其在驱动适应性免疫反应中作用的认识。
