Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2012 Sep 7;425(4):918-23. doi: 10.1016/j.bbrc.2012.08.010. Epub 2012 Aug 12.
To maintain immune homeostasis in the intestine, the intestinal immune system has evolved several tolerogenic mechanisms toward intestinal microflora and food antigens. Although programmed cell death-1 (PD-1) protein has been implicated in immunological tolerance in the intestine and gut-associated lymphoid tissues (GALTs), distribution of its ligands PD-L1 and PD-L2 in the small intestine lamina propria (LP) are unknown. We investigated PD-L1 expression in intestinal LP and found that IgA plasma cells (PCs) were major PD-L1 expressing cells. PD-L1 expression levels on IgA PCs were higher than that on IgG PCs in peripheral lymphoid tissues. IgA PCs expressed antigen-presenting molecule MHC class II and co-stimulatory molecules CD80, CD86, and PD-L2. IgA PCs isolated from intestinal LP exhibited antigen presentation activity, and in the presence of TGF-β induced FoxP3(+) regulatory T cells, but not IFN-γ(+) Th1 cells, from naïve T cells. Thus, IgA PCs in the intestine may be involved in an immune regulatory role in the intestinal immune system.
为了维持肠道内的免疫稳态,肠道免疫系统已经进化出几种针对肠道微生物群和食物抗原的耐受机制。尽管程序性细胞死亡蛋白 1(PD-1)蛋白已被牵涉到肠道和肠道相关淋巴组织(GALTs)中的免疫耐受,但 PD-1 的配体 PD-L1 和 PD-L2 在小肠固有层(LP)中的分布尚不清楚。我们研究了 PD-L1 在肠道 LP 中的表达,发现 IgA 浆细胞(PCs)是主要的 PD-L1 表达细胞。IgA PCs 上的 PD-L1 表达水平高于外周淋巴组织中的 IgG PCs。IgA PCs 表达抗原呈递分子 MHC Ⅱ类和共刺激分子 CD80、CD86 和 PD-L2。从肠道 LP 分离出的 IgA PCs 表现出抗原呈递活性,并且在 TGF-β诱导的 FoxP3(+)调节性 T 细胞,但不是 IFN-γ(+)Th1 细胞,从幼稚 T 细胞中产生。因此,肠道中的 IgA PCs 可能参与肠道免疫系统的免疫调节作用。