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神经损伤诱导蛋白 1 在肠道炎症条件下对髓系细胞的有害作用。

Detrimental Role of Nerve Injury-Induced Protein 1 in Myeloid Cells under Intestinal Inflammatory Conditions.

机构信息

Interdisciplinary Program in Cancer Biology, College of Medicine, Seoul National University, Seoul 03080, Korea.

Korea Mouse Phenotyping Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

出版信息

Int J Mol Sci. 2020 Jan 17;21(2):614. doi: 10.3390/ijms21020614.

Abstract

Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell-surface adhesion molecule that regulates cell migration and attachment. This study demonstrates the increase in Ninj1 protein expression during development of intestinal inflammation. Ninj1-deficient mice exhibited significantly attenuated bodyweight loss, shortening of colon length, intestinal inflammation, and lesser pathological lesions than wild-type mice. Although more severe inflammation and serious lesions are observed in wild-type mice than Ninj1-deficient mice, there were no changes in the numbers of infiltrating macrophages in the inflamed tissues obtained from WT and Ninj1-deficient mice. Ninj1 expression results in activation of macrophages, and these activated macrophages secrete more cytokines and chemokines than Ninj1-deficient macrophages. Moreover, mice with conditional deletion of Ninj1 in myeloid cells (Ninj1; Lyz-Cre+) alleviated experimental colitis compared with wild-type mice. In summary, we propose that the Ninj1 in myeloid cells play a pivotal function in intestinal inflammatory conditions.

摘要

神经损伤诱导蛋白 1(Ninjurin1,Ninj1)是一种细胞表面黏附分子,可调节细胞迁移和黏附。本研究表明,Ninj1 蛋白表达在肠道炎症发生过程中增加。Ninj1 缺陷型小鼠的体重减轻、结肠缩短、肠道炎症以及病理损伤明显低于野生型小鼠。尽管野生型小鼠的炎症比 Ninj1 缺陷型小鼠更严重,病变更严重,但在来自 WT 和 Ninj1 缺陷型小鼠的炎性组织中浸润的巨噬细胞数量没有变化。Ninj1 表达导致巨噬细胞活化,这些活化的巨噬细胞分泌的细胞因子和趋化因子比 Ninj1 缺陷型巨噬细胞多。此外,髓样细胞中 Ninj1 条件性缺失(Ninj1;Lyz-Cre+)的小鼠与野生型小鼠相比,实验性结肠炎得到缓解。总之,我们提出髓样细胞中的 Ninj1 在肠道炎症状态下发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da8/7013940/9470ee279110/ijms-21-00614-g001.jpg

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