Effect of tick saliva cystatins on Th9 cells, mast cells and the development of experimental asthma

壁虱唾液中含有一系列免疫调节分子，便于血液喂养和壁虱传播病原体。基于硬蜱唾液腺的cDNA文库，部分分子已被鉴定并通过重组表达制备。蓖麻硬蜱的唾液和唾液抑制素L，一种从相关的扁虱唾液中分离出来的胱抑素，出人意料地抑制了白细胞介素9(IL-9)的产生。由于IL-9在过敏性哮喘的发生发展中起核心作用，我们在小鼠哮喘模型的致敏阶段给予唾液酸抑素L，并在初步实验中发现它抑制了这种疾病的发展。由于我们的初步数据表明，唾液酸抑制素L对肥大细胞和Th9细胞产生IL-9有实质性的抑制能力，因此我们将主要关注这类半胱氨酸氨基转移酶的抑制机制(S)。特别分析了半胱氨酸氨基转移酶对Th9细胞和肥大细胞动态组的影响。或者，Th9细胞和肥大细胞的表达谱将通过下一代测序(NGS)在没有和存在抑制性半胱氨酸类药物的情况下确定。最终，所获得的结果将被用于开发从扁虱唾液中提取特定的IL-9调节分子来治疗过敏性疾病和哮喘的创新治疗策略。

Tick saliva contains an array of immunomodulatory molecules facilitating both blood feeding and tick-borne pathogen transmission. Based on cDNA library of tick salivary glands, some of these molecules have been identified and prepared by recombinant expression. Ixodes ricinus tick saliva and sialostatin L, a cystatin isolated from saliva of the related tick I. scapularis, surprisingly inhibited production of interleukin 9 (IL-9). As IL-9 plays a central role in the development of allergic asthma, we administered sialostatin L during the sensitization phase in a murine asthma model and found in pilot experiments that it inhibits the development of this disease. Since our preliminary data demonstrated that sialostatin L has a substantial inhibitory capacity on the IL-9 production of mast cells and Th9 cells, we will primarily focus on the inhibitory mechanism(s) of such cystatins. Especially, the influence of cystatins on the kinome of Th9 cells and mast cells will be analyzed. Alternatively, expression profiles of Th9 cells and mast cells will be determined by next-generation sequencing (NGS) in the absence and presence of inhibitory cystatins. Eventually, the obtained results will be used to develop innovative therapeutic strategies for the treatment of allergic diseases and asthma by exploiting definite IL-9 modulating molecules from tick saliva.