Wang Haifang, Zhang Xinwen, Zuo Zhanguang, Zhang Qin, Pan Ying, Zeng Benhua, Li Wenxia, Wei Hong, Liu Zhihua
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
J Immunol. 2017 May 1;198(9):3729-3736. doi: 10.4049/jimmunol.1601583. Epub 2017 Mar 22.
Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2. Thus, we delineated a genetic pathway, consisting of Nod2-LRRK2-Rip2-Rab2a, which is required for lysozyme sorting. Taken together, our results indicate that the lysozyme-sorting process in Paneth cells is orchestrated by a number of host factors and highlight the importance of Paneth cell function in intestinal homeostasis.
潘氏细胞通过向肠腔分泌大量抗菌肽在维持肠道内环境稳定中发挥重要作用。在本研究中，我们发现Rip2以依赖于Nod2、LRRK2和Rab2a的方式参与潘氏细胞中溶菌酶的分选。小鼠中Rip2缺乏导致潘氏细胞中溶菌酶的溶酶体降解，并阻止Rab2a募集到致密核心囊泡（DCV）上。与Nod2和LRRK2一样，Rip2定位于潘氏细胞的DCV，其DCV定位依赖于Nod2和LRRK2。因此，我们描绘了一条由Nod2-LRRK2-Rip2-Rab2a组成的基因途径，这是溶菌酶分选所必需的。综上所述，我们的结果表明潘氏细胞中的溶菌酶分选过程由多种宿主因子协调，并突出了潘氏细胞功能在肠道内环境稳定中的重要性。
