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

髓系抑制细胞和 γδT17 细胞促进猫嗜血杆菌感染小鼠胃 MALT 淋巴瘤的发生

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作者:Yanan Zhao, Fei Lu, Jingjing Ye, Min Ji, Yihua Pang, Yan Wang, Lingbo Wang, Guosheng Li, Tao Sun, Jingxin Li, Daoxin Ma, Chunyan Ji

Abstract

Helicobacter-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 Helicobacter felis-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 H. felis-infected stomach. Persistent H. felis 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.

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