Regulation of human enteric α-defensins by NOD2 in the Paneth cell lineage
Regulation of human enteric α-defensins by NOD2 in the Paneth cell lineage
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潘氏细胞谱系中 NOD2 对人肠道 α 防御素的调节
DOI：
10.1016/j.ejcb.2014.10.007
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发表时间：
2015-01-01
影响因子：
6.6
通讯作者：
Zhi, Fa-Chao
中科院分区：
文献类型：
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作者：
Tan, Gao;Zeng, Bin;Zhi, Fa-Chao
人肠α-防御素（HD5和HD6）是肠道潘氏细胞产生的主要抗菌肽，在肠道先天免疫中发挥重要作用。由于它们的表达在克罗恩病 (CD) 中降低，并且在 NOD2 突变存在时表达降低更为明显，因此研究 NOD2 调节人肠道 α-防御素表达的机制将非常有趣。在这里，我们发现，虽然NOD2本身主要通过激活NF-κB途径轻微上调肠α-防御素的表达，但它主要通过抑制MAPK途径的激活，在潘氏细胞谱系分化过程中强烈下调肠α-防御素的表达。由于 NOD2 在 CD 中过度表达，并且突变型 NOD2 不能导致 NF-κ B 活性，因此我们的发现可以解释先前的观察结果，即 CD 中人肠道 α-防御素表达降低，在 NOD2 突变存在的情况下更是如此。此外，这一发现为NOD2调节肠道先天免疫的功能提供了新的观点。 (C) 2014 年爱思唯尔有限公司。版权所有。
Human enteric alpha-defensins (HD5 and HD6), major antimicrobial peptides produced by Paneth cells in the intestine, play important roles in intestinal innate immunity. Since their expression is decreased in Crohn's disease (CD), with decreased expression being more pronounced in the presence of NOD2 mutations, it would be extremely interesting to investigate the mechanism by which NOD2 may regulate expression of human enteric a-defensins. Here we show that although NOD2 by itself can slightly up-regulate expression of enteric a-defensins mainly through activation of the NF-kappa B pathway, it can strongly down-regulates their expression during differentiation of the Paneth cell lineage mainly by inhibiting activation of the MAPK pathway. Since NOD2 is over-expressed in CD and mutant NOD2 cannot result in NF-kappa B activity, our finding can provide an explanation of the previous observation showing decreased expression of human enteric a-defensin in CD and even more so in the presence of NOD2 mutations. In addition, this finding provides a new view on the function of NOD2 in regulating intestinal innate immunity. (C) 2014 Elsevier GmbH. All rights reserved.