Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Genes Cells. 2010 Dec;15(12):1189-200. doi: 10.1111/j.1365-2443.2010.01453.x. Epub 2010 Oct 28.
Mononuclear phagocytes such as dendritic cells (DCs) and macrophages in the lamina propria (LP) are thought to be important for both induction of inflammatory responses and maintenance of immunologic tolerance in the mammalian intestine. The molecular mechanisms by which these cells regulate intestinal immunity have remained poorly understood, however. Signal regulatory protein α (SIRPα) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils. Here, we show that SIRPα is abundant in CD11c(+) CD11b(+) LP cells of the mouse intestine. Whereas SIRPα did not appear to be important for the steady-state homeostasis of mucosal immunity in the intestine, the flagellin-stimulated production of IL-17 or interferon (IFN)-γ by LP cells of SIRPα mutant (MT) mice that lack the cytoplasmic region of the protein was markedly decreased compared with that observed with wild-type cells. Moreover, the flagellin-induced production of IL-6 by LP cells from SIRPα MT mice was also greatly reduced. SIRPα MT mice were also resistant to the development of colitis induced by IL-10 deficiency. Our data thus suggest that SIRPα expressed on CD11c(+) LP cells is important for the production of IL-17 or IFN-γ in the LP as well as for the development of colitis induced by IL-10 deficiency.
单核吞噬细胞，如树突状细胞 (DCs) 和固有层 (LP) 中的巨噬细胞，被认为对哺乳动物肠道中炎症反应的诱导和免疫耐受的维持都很重要。然而，这些细胞调节肠道免疫的分子机制仍知之甚少。信号调节蛋白 α (SIRPα) 是一种跨膜蛋白，特异性表达于 DCs、巨噬细胞和中性粒细胞。在这里，我们显示 SIRPα 在小鼠肠道的 CD11c(+) CD11b(+) LP 细胞中丰富表达。虽然 SIRPα 似乎对肠道黏膜免疫的稳态平衡不重要，但缺乏该蛋白胞质区的 SIRPα 突变体 (MT) 小鼠 LP 细胞中，鞭毛蛋白刺激产生的 IL-17 或干扰素 (IFN)-γ 的水平明显低于野生型细胞。此外，SIRPα MT 小鼠 LP 细胞中鞭毛蛋白诱导的 IL-6 产生也大大减少。SIRPα MT 小鼠也对由 IL-10 缺乏引起的结肠炎的发展具有抗性。因此，我们的数据表明，CD11c(+) LP 细胞上表达的 SIRPα 对于 LP 中 IL-17 或 IFN-γ 的产生以及由 IL-10 缺乏引起的结肠炎的发展都很重要。
