Background: Ulcerative colitis (UC) is a progressive chronic inflammatory disorder. Neutrophils play a critical role in regulating intestinal mucosal homeostasis in UC. Spleen tyrosine kinase (Syk) is involved in several inflammatory diseases. Here, we evaluated the effects and underlying mechanisms of Syk on neutrophil immune-responses in UC. Methods: Syk expression in the colonic tissues of patients with UC was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. Colonic biopsies from patients with UC were obtained for single-cell RNA-sequencing. Neutrophils isolated from peripheral blood were pre-treated with R788 (a Syk inhibitor) and gene differences were determined using RNA sequencing. Neutrophil functions were analyzed using qRT-PCR, flow cytometry, and Transwell assay. R788 was administered daily to mice with dextran sulfate sodium (DSS)-induced colitis to verify the effects of Syk on intestinal inflammation. Results: Syk expression was increased in inflamed mucosa and neutrophils of patients with UC and positively correlated with disease activity. Pharmacological inhibition of Syk in neutrophils decreased the production of pro-inflammatory cytokines, chemokines, neutrophil extracellular traps, reactive oxygen species, and myeloperoxidase. Apoptosis and migration of neutrophils were suppressed by Syk blockade. Syk blockade ameliorated mucosal inflammation in DSS-induced murine colitis by inhibiting neutrophil-associated immune responses. Mechanistically, Syk regulated neutrophil immune-responses via the mammalian target of rapamycin kinase/rubicon-like autophagy enhancer-dependent autophagy pathway. Conclusions: Our findings indicate that Syk facilitates specific neutrophil functional responses to mucosal inflammation in UC, and its inhibition ameliorates mucosal inflammation in DSS-induced murine colitis, suggesting its potential as a novel therapeutic target for UC treatment. Keywords: Syk; UC; autophagy; neutrophils.

---

 

乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。