Role of SIRPα in regulation of mucosal immunity in the intestine
Role of SIRPα in regulation of mucosal immunity in the intestine
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DOI：
10.1111/j.1365-2443.2010.01453.x
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发表时间：
2010-12-01
期刊：
影响因子：
2.1
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
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作者：
Kanazawa, Yoshitake;Saito, Yasuyuki;Matozaki, Takashi
固有层 (LP) 中的树突状细胞 (DC) 和巨噬细胞等单核吞噬细胞被认为对于诱导哺乳动物肠道炎症反应和维持免疫耐受非常重要。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，在DC、巨噬细胞和中性粒细胞中特异性表达。在这里，我们发现 SIRP α 在小鼠肠道的 CD11c+ CD11b+ LP 细胞中含量丰富。虽然 SIRP α 似乎对肠道粘膜免疫的稳态稳态并不重要，但与野生型细胞相比，缺乏蛋白质细胞质区域的 SIRP α 突变体 (MT) 小鼠的 LP 细胞鞭毛蛋白刺激的 IL-17 或干扰素 (IFN)-γ 的产生明显减少。此外，SIRP α MT 小鼠的 LP 细胞鞭毛蛋白诱导的 IL-6 产生也大大减少。 SIRP α MT 小鼠也能抵抗 IL-10 缺乏引起的结肠炎的发展。因此，我们的数据表明，CD11c+ LP 细胞上表达的 SIRP α 对于 LP 中 IL-17 或 IFN-γ 的产生以及 IL-10 缺乏引起的结肠炎的发展很重要。
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 alpha (SIRP alpha) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils. Here, we show that SIRP alpha is abundant in CD11c+ CD11b+ LP cells of the mouse intestine. Whereas SIRP alpha 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)-gamma by LP cells of SIRP alpha 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 SIRP alpha MT mice was also greatly reduced. SIRP alpha MT mice were also resistant to the development of colitis induced by IL-10 deficiency. Our data thus suggest that SIRP alpha expressed on CD11c+ LP cells is important for the production of IL-17 or IFN-gamma in the LP as well as for the development of colitis induced by IL-10 deficiency.