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单细胞中的NOD2通过TNFalpha负面调节巨细胞的发育

Camille Chauvin^1,2, Daniel Alvarez-Simon¹, Katarina Radulovic³

¹U1019, Institut Pasteur de Lille, Univ. Lille, Centre National de la Recherche Scientifique, Inserm, Centre Hospitalo- Universitaire Lille, Lille, France.

Frontiers in immunology

|July 7, 2023

概括

通常情况下,NOD2会抑制肠道中巨细胞与单细胞的分化. 克罗恩氏病 (CD) 患者的NOD2功能丧失可能会损害这种调节,可能会影响治疗策略.

科学领域:

免疫学免疫学免疫学
胃肠病学胃肠病学
细胞生物学细胞生物学

背景情况:

克罗恩氏病 (CD) 与NOD2风险等位基因有关,目前的理论表明单细胞招募导致致病性巨细胞.
另一个假设是NOD2可能会抑制单细胞分化成巨细胞.

研究的目的:

研究NOD2在调节单细胞分化成肠道巨细胞中的作用.
探索NOD2功能在CD中的潜在治疗影响.

主要方法:

使用无菌小鼠,混合骨髓仿真体和体外培养系统.
检查了单细胞衍生的树突细胞 (mo-DCs) 和巨细胞的分化.
采用药理抑制剂并分析了对muramyl dipeptide (MDP) 的反应.

主要成果:

缺少NOD2导致结肠中mo-DC频率降低,独立于微生物群变化.
在NOD2缺乏的骨髓嵌合体中观察到受损的mo-DC复制.
NOD2激活通过TNFα依赖的途径抑制mTOR介导的巨细胞分化,这一过程被NOD2突变破坏.

结论:

NOD2通过前循环负面调节巨细胞的发育.
这种调节途径是克服CD中抗TNF治疗的抗性治疗的潜在目标.

关键词:

在NOD2中,NOD2是NOD2.这就是TNF-α.大肠炎是一种大肠炎.在mTOROR中使用mTOR.巨细胞是什么?巨细胞是什么?我们的微生物群.在mo-DCs中使用.单细胞 (Monocytes) 是一种单细胞.

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