模式识别受体 NOD2 调节人类 FOXP3+T 细胞存活。
The pathogen recognition receptor NOD2 regulates human FOXP3+ T cell survival.
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
出版信息
J Immunol. 2010 Jun 15;184(12):7247-56. doi: 10.4049/jimmunol.0901479. Epub 2010 May 7.
The expression of pathogen recognition receptors in human FOXP3+ T regulatory cells is established, yet the function of these receptors is currently obscure. In the process of studying the function of both peripheral and lamina propria FOXP3+ lymphocytes in patients with the human inflammatory bowel disease Crohn's disease, we observed a clear deficiency in the quantity of FOXP3+ lymphocytes in patients with disease-associated polymorphisms in the pathogen recognition receptor gene NOD2. Subsequently, we determined that the NOD2 ligand, muramyl dipeptide (MDP), activates NF-kappaB in primary human FOXP3+ T cells. This activation is functionally relevant, as MDP-stimulated human FOXP3+ T cells are protected from death receptor Fas-mediated apoptosis. Importantly, apoptosis protection was not evident in MDP-stimulated FOXP3+ T cells isolated from a patient with the disease-associated polymorphism. Thus, we propose that one function of pathogen recognition receptors in human T regulatory cells is the protection against death receptor-mediated apoptosis in a Fas ligand-rich environment, such as that of the inflamed intestinal subepithelial space.
病原体识别受体在人 FOXP3+T 调节细胞中的表达已经确定，但这些受体的功能目前尚不清楚。在研究人类炎症性肠病克罗恩病患者外周和固有层 FOXP3+淋巴细胞的功能的过程中，我们观察到在与病原体识别受体基因 NOD2 相关的疾病多态性的患者中，FOXP3+淋巴细胞的数量明显减少。随后，我们确定病原体识别受体 NOD2 的配体，即 muramyl dipeptide（MDP），可以激活原代人 FOXP3+T 细胞中的 NF-κB。这种激活具有功能相关性，因为 MDP 刺激的人 FOXP3+T 细胞可以免受死亡受体 Fas 介导的细胞凋亡。重要的是，在携带疾病相关多态性的患者中分离出的 MDP 刺激的 FOXP3+T 细胞中，并没有明显的细胞凋亡保护作用。因此，我们提出，病原体识别受体在人类 T 调节细胞中的一个功能是在 Fas 配体丰富的环境中，如炎症性肠上皮下空间，防止死亡受体介导的细胞凋亡。
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