加勒7导致CD4+T细胞的相对减少,PD-1介导
Guojin Wu1, Wei Deng2, Hsin-Yi Chen1
1Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9072, USA.
Scientific reports
|March 20, 2024
概括
加勒7通过与PD-1结合来减少CD4+T细胞,从而影响癌症中的免疫调节. 这种通过PD-1糖化介导的相互作用突出了免疫调节的新治疗标.
科学领域:
- 免疫学 免疫学 免疫学
- 葡萄糖生物学 葡萄糖生物学
- 癌症研究 癌症研究
背景情况:
- 葡萄糖结合蛋白因其调节免疫反应的作用而越来越被认可.
- 免疫调节受体,如PD-1,是癌症免疫治疗的关键目标.
- galectins 与免疫检查点相互作用的具体机制尚未完全理解.
研究的目的:
- 研究加勒7在调节CD4+T细胞种群中的作用.
- 阐明加勒素7与编程细胞死亡蛋白1 (PD-1) 受体之间的相互作用.
- 探索加勒7与PD-1糖化位的结合的功能后果.
主要方法:
- 实验室细胞培养和小鼠瘤模型被用于评估CD4+T细胞百分比.
- 消化管癌患者样本的免疫组合化学染色分析了加勒7和CD4+细胞的同定位.
- 结合性测试,PD-1淘汰赛小鼠模型和siRNA介导的PD-1抑制被用于研究加勒素7-PD-1相互作用.
- 在加勒7治疗后评估了SHP-2招募和NFAT活性.
主要成果:
- 加勒素7在体外和体内显著降低了CD4+T细胞百分比.
- 在食道癌组织中,较低的CD4+T细胞计数与高的加勒7表达相关.
- 证实了加勒素7与PD-1的N-糖化位点 (N74,N116) 的结合,导致了SHP-2的招募.
- 抑制PD-1或SHP-2废除的加勒素7的NFAT抑制活性.
结论:
- 加勒7作为CD4+T细胞功能的抑制剂,可能通过其与PD-1的相互作用.
- PD-1的N-糖化对加勒素7结合和随后的免疫调节至关重要.
- 这项研究揭示了一种新的免疫调节机制,涉及加勒7和PD-1糖化,这表明了潜在的治疗策略.
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