The potential role of Osteopontin in the maintenance of commensal bacteria homeostasis in the intestine.
The potential role of Osteopontin in the maintenance of commensal bacteria homeostasis in the intestine.
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DOI：
10.1371/journal.pone.0173629
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Hattori M
中科院分区：
文献类型：
--
作者：
Ito K;Nakajima A;Fukushima Y;Suzuki K;Sakamoto K;Hamazaki Y;Ogasawara K;Minato N;Hattori M
骨桥蛋白（Osteopontin，Opn）是一种多功能的细胞外基质蛋白，参与多种炎症性疾病的发病机制。在生理条件下，其表达仅限于某些组织，包括骨和肾小管。然而，疾病发展期间的细胞活化诱导各种免疫细胞中的Opn表达。在这项研究中，使用Opn-EGFP敲入（KI）小鼠，我们发现肠道组织中的CD 8 α+ T细胞，包括派伊尔结，固有层和上皮细胞，在稳态条件下表达Opn。因此，我们研究了表达Opn的CD 8 α+ T细胞在肠道稳态中的作用。有趣的是，Opn敲除（KO）小鼠具有与TCRγδ+上皮内淋巴细胞（IEL）减少一致的改变的粪便微生物区系。与该结果一致，用抗Opn阻断抗体处理和Opn缺乏均导致TCRγδ+和TCRαβ+ IEL的存活降低。该数据表明Opn可能作为肠组织中IEL的存活因子起作用。总的来说，这些数据表明Opn可能通过维持TCRγδ+ IEL来调节肠道微生物群落的稳态，可能是通过支持IEL存活。
Osteopontin (Opn), a multifunctional extracellular matrix protein, is implicated in the pathogenesis of various inflammatory disorders. Under physiologic conditions, its expression is restricted to certain tissues including bone and kidney tubule. However, cellular activation during disease development induces Opn expression in various immune cells. In this study, using Opn-EGFP knock-in (KI) mice we found that CD8α+ T cells in the intestinal tissues, including Peyer’s patch, lamina propria and epithelium, express Opn under steady state conditions. Therefore, we examined the role of Opn-expressing CD8α+ T cells in intestinal homeostasis. Interestingly, Opn knockout (KO) mice had altered fecal microflora concordant with a reduction of TCRγδ+ intraepithelial lymphocytes (IELs). Consistent with this result, both treatment with anti-Opn blocking antibody and deficiency of Opn resulted in decreased survival of TCRγδ+ and TCRαβ+ IELs. This data suggests that a possibility that Opn may function as a survival factor for IELs in the intestinal tissue. Collectively, these data suggest the possibility that Opn might regulate the homeostasis of intestinal microflora through maintenance of TCRγδ+ IELs, possibly by support of IEL survival.