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骨髓来源的抑制细胞和 γδT17 细胞有助于感染小鼠胃黏膜相关淋巴组织淋巴瘤的发展。

Myeloid-Derived Suppressor Cells and γδT17 Cells Contribute to the Development of Gastric MALT Lymphoma in -Infected Mice.

机构信息

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.

Department of Hematology, Taian Central Hospital, Taian, China.

出版信息

Front Immunol. 2020 Jan 28;10:3104. doi: 10.3389/fimmu.2019.03104. eCollection 2019.

Abstract

-induced chronic inflammation and immune disorders are closely associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Myeloid-derived suppressor cells (MDSCs) exhibit strong immunosuppressive properties and promote the growth of various solid tumors. However, the role of MDSCs in the development of MALT lymphoma has not been elucidated so far. We detected significant infiltration and enrichment of MDSCs in patients with MALT lymphoma, as well in -infected mouse model of gastric MALT lymphoma. In addition, the expression of arginase-1 and inducible nitric oxide synthase was significantly elevated both in gastric MALT lymphoma tissues and -infected stomach. Persistent infection closely reproduced the development of gastric MALT lymphoma and was accompanied by increased numbers of γδT17 cells. Accumulation of γδT17 cells was also validated in the human gastric MALT lymphoma tissues. Furthermore, the elevated cytokines interleukin-23 and interleukin-1β, as well as chemokines CCL20/CCR6, may be involved in the accumulation of γδT17 cells and the subsequent immunosuppression. These findings highlight the role of MDSCs and γδT17 cells in immune dysregulation during gastric MALT lymphoma development and their potential as therapeutic targets.

摘要
  • 诱导的慢性炎症和免疫紊乱与胃黏膜相关淋巴组织 (MALT) 淋巴瘤的发展密切相关。髓源抑制细胞 (MDSC) 具有很强的免疫抑制特性,并促进各种实体瘤的生长。然而,MDSC 在 MALT 淋巴瘤发展中的作用迄今尚未阐明。我们在 MALT 淋巴瘤患者以及感染性胃 MALT 淋巴瘤小鼠模型中检测到 MDSC 的显著浸润和富集。此外,在胃 MALT 淋巴瘤组织和感染的胃中,精氨酸酶-1 和诱导型一氧化氮合酶的表达均显著升高。持续感染密切再现了胃 MALT 淋巴瘤的发展,并伴有 γδT17 细胞数量的增加。γδT17 细胞的积累也在人类胃 MALT 淋巴瘤组织中得到了验证。此外,升高的细胞因子白细胞介素-23 和白细胞介素-1β以及趋化因子 CCL20/CCR6 可能参与了 γδT17 细胞的积累和随后的免疫抑制。这些发现强调了 MDSC 和 γδT17 细胞在胃 MALT 淋巴瘤发展过程中免疫失调中的作用及其作为治疗靶点的潜力。

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