RGS10 缺陷通过抑制溃疡性结肠炎患者的 Th1/Th17 细胞免疫反应缓解肠粘膜炎症

IF 4.9 3区 医学 Q2 IMMUNOLOGY
Immunology Pub Date : 2024-10-20 DOI:10.1111/imm.13869
Yonghong Yang, Yiming Shao, Xizhuang Gao, Zongjing Hu, Yan Wang, Cuimei Ma, Guiyuan Jin, Fengqin Zhu, Guanjun Dong, Guangxi Zhou
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引用次数: 0

摘要

G 蛋白信号调节器(RGS)10 在多种免疫相关疾病中发挥着关键作用。然而,RGS10是否参与了溃疡性结肠炎(UC)的结肠炎症仍不清楚。本研究旨在探讨 RGS10 在 UC 中的作用。本研究通过实时定量聚合酶链式反应(qRT-PCR)、免疫印迹、免疫组织化学和免疫荧光分析检测了RGS10的表达。对肠粘膜进行了单细胞 RNA 测序,以确定 RGS10 有不同表达的关键免疫细胞。RGS10基因敲除小鼠在葡聚糖硫酸钠(DSS)诱导的结肠炎中发病。通过 qRT-PCR、酶联免疫吸附试验和流式细胞术检测了炎症细胞因子在 mRNA 和蛋白质水平上的表达。我们发现,与健康人相比,UC 患者的 RGS10 表达明显升高,尤其是在 CD4+ T 细胞中。耐人寻味的是,RGS10 的缺乏明显缓解了 DSS 诱导的结肠炎,并降低了固有膜单核细胞(LPMCs)、外周血(PB)、脾脏和肠系膜淋巴结(mLNs)中 Th1 和 Th17 细胞的比例。从机理上讲,RGS10 缺乏会抑制信号转导和转录激活因子(STAT)1 和 STAT3 的磷酸化,从而阻止 Th1 和 Th17 细胞的分化。共免疫沉淀分析进一步表明,RGS10能与蛋白酪氨酸磷酸酶非受体2型(PTPN2)相互作用,并进一步调控CD4+ T细胞的Th1和Th17细胞分化。总之,RGS10缺乏可通过与CD4+ T细胞中的PTPN2相互作用,抑制Th1/Th17细胞介导的免疫反应,从而缓解肠粘膜炎症。因此,靶向 RGS10 可能是治疗 UC 的一种新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RGS10 Deficiency Alleviated Intestinal Mucosal Inflammation Through Suppression of Th1/Th17 Cell Immune Responses in Ulcerative Colitis.

Regulator of G-protein signalling (RGS) 10 plays critical roles in several immune related diseases. However, whether RGS10 is involved in colonic inflammation of ulcerative colitis (UC) is still obscure. This study aimed to investigate the role of RGS10 in UC. In this study, RGS10 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and immunofluorescent analysis. Single-cell RNA sequencing of intestinal mucosa was performed to identify key immune cells with differentially expressed RGS10. RGS10 knockout mice were generated and established dextran sulphate sodium (DSS)-induced colitis. Expression of inflammatory cytokines on mRNA and protein levels was detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. We found that RGS10 expression was significantly elevated in UC patients, especially in CD4+ T cells, compared with healthy subjects. Intriguingly, RGS10 deficiency markedly alleviated DSS-induced colitis and decreased the proportion of Th1 and Th17 cells in lamina propria mononuclear cells (LPMCs), peripheral blood (PB), spleens, and mesenteric lymph nodes (mLNs). Mechanistically, RGS10 deficiency blocked the differentiation of Th1 and Th17 cells by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3. The co-immunoprecipitation analysis further showed that RGS10 could interact with protein tyrosine phosphatase non-receptor type 2 (PTPN2), and further regulated Th1 and Th17 cells differentiation of CD4+ T cells. In conclusion, RGS10 deficiency alleviated intestinal mucosal inflammation through inhibition of Th1/Th17 cell-mediated immune responses via interaction with PTPN2 in CD4+ T cells. Therefore, targeting RGS10 may represent a novel therapeutic approach for UC treatment.

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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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