Ito cells are liver-resident antigen-presenting cells for activating T cell responses
Ito cells are liver-resident antigen-presenting cells for activating T cell responses
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DOI：
10.1016/j.immuni.2006.11.011
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发表时间：
2007-01-01
期刊：
影响因子：
32.4
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
--
作者：
Winau, Florian;Hegasy, Guido;Kaufmann, Stefan H. E.
在这里，我们确定了伊藤细胞（肝星状细胞，HSC），已知的维生素A的存储和参与肝纤维化，作为专业的肝脏常驻抗原呈递细胞（APC）。Ito细胞有效地将抗原呈递给CD 1-、主要组织相容性复合体（MHC）-I-和MHC-II-限制性T细胞。Ito细胞向CD 1限制性T淋巴细胞（如自然杀伤T（NKT）细胞）呈递脂质抗原，并通过白细胞介素-15促进肝脏NKT细胞的稳态增殖。此外，Ito细胞将抗原肽呈递给CD 8（+）和CD 4（+）T细胞，并介导CD 8（+）T细胞的交叉印迹。肽特异性T细胞被呈递内源性新抗原的转基因Ito细胞激活。在细菌感染后，Ito细胞引发抗原特异性T细胞并介导保护作用。与其他参与诱导免疫耐受的肝细胞类型相反，我们的数据将Ito细胞鉴定为专业的肝内APC，其激活T细胞并引发多种对蛋白质和脂质抗原特异性的T细胞应答。
Here we identified Ito cells (hepatic stellate cells, HSC), known for storage of vitamin A and participation in hepatic fibrosis, as professional liver-resident antigen-presenting cells (APC). Ito cells efficiently presented antigens to CD1-, major histocompatibility complex (MHC)-I-, and MHC-II-restricted T cells. Ito cells presented lipid antigens to CD1-restricted T lymphocytes such as natural killer T (NKT) cells and promoted homeostatic proliferation of liver NKT cells through interieukin-15. Moreover, Ito cells presented antigenic peptides to CD8(+) and CD4(+) T cells and mediated crosspriming of CD8(+) T cells. Peptide-specific T cells were activated by transgenic Ito cells presenting endogenous neoantigen. Upon bacterial infection, Ito cells elicited antigen-specific T cells and mediated protection. In contrast to other liver cell types that have been implicated in induction of immunological tolerance, our data identify Ito cells as professional intrahepatic APCs activating T cells and eliciting a multitude of T cell responses specific for protein and lipid antigens.