LRCH1 suppresses migration of CD4+ T cells and refers to disease activity in ulcerative colitis
LRCH1 suppresses migration of CD4+ T cells and refers to disease activity in ulcerative colitis
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DOI：
10.7150/ijms.39106
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Zhou, Guangxi
中科院分区：
文献类型：
--
作者：
Wang, Yibo;Zhang, Hairong;Zhou, Guangxi
背景：溃疡性结肠炎（UC）是一种慢性进行性炎症性疾病。据报道，LRCH 1参与多种疾病的免疫调节。材料与方法：采用定量RT-PCR和免疫组化方法检测UC患者炎症黏膜和外周血单个核细胞（PBMCs）中LRCH 1的表达。用表达LRCH 1的慢病毒（LV-LRCH 1）或LV-sh-LRCH 1转染外周血CD 4（+）T细胞，通过流式细胞术、定量RT-PCR和ELISA检测细胞因子的表达。结果：LRCH 1在A-UC患者结肠黏膜和PBMC中的表达明显降低，且与疾病活动性呈负相关。上调或下调LRCH 1表达均不影响CD 4（+）T细胞的分化及相关细胞因子的表达。结论：LRCH 1可能通过调节CD 4（+）T细胞向CXCL 12的迁移，在UC的发病机制中起重要作用。因此，靶向LRCH 1可能成为UC管理的新治疗方法。
Background: Ulcerative colitis (UC) is a chronically remittent and progressive inflammatory disorder. LRCH1 is reported to be involved in the immune-regulation of several diseases. However, the exact roles of LRCH1 in UC are still obscure.Materials and Methods: LRCH1 expression was analyzed in the inflamed mucosa and peripheral blood mononuclear cells (PBMCs) from patients with UC by quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4(+) T cells were transfected with lentivirus-expressing LRCH1 (LV-LRCH1) or LV-sh-LRCH1, and cytokine expression was determined by using flow cytometry, quantitative RT-PCR and ELISA. Transfected CD4(+) T cells were harvested to examine the capacity of chemotaxis using Transwell plate.Results: LRCH1 expression was highly decreased in colonic mucosa and PBMCs from patients with A-UC, and negatively correlated with disease activity. Up or down regulation of LRCH1 did not affect the differentiation of CD4(+) T cells, and the related cytokines expression. Moreover, LRCH1 inhibited migratory capacity of CD4(+) T cells toward CXCL12 by PKCA alpha.Conclusion: LRCH1 plays an important role in the pathogenesis of UC, possibly through modulating the migration of CD4(+) T cells. Therefore, targeting LRCH1 might serve as a novel therapeutic approach in the management of UC.