A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.
A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.
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DOI：
10.1038/nature07537
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发表时间：
2009-02-05
期刊：
影响因子：
64.8
通讯作者：
Colonna, Marco
中科院分区：
文献类型：
--
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
自然杀伤（NK）细胞通常被视为淋巴细胞，其通过释放溶细胞介质和IFN-γ来提供针对病毒感染的细胞和肿瘤细胞的先天监视。在人类中，血液CD 56 dim NK细胞专门裂解细胞靶标。在淋巴结中，CD 56 bright NK细胞分泌IFN-γ，与树突状细胞（DC）和T细胞合作产生适应性应答。在这里，我们报告了位于粘膜相关淋巴组织（MALT），如扁桃体和派氏斑，这是硬连线分泌白细胞介素（IL）-22，IL-26和白血病抑制因子（LIF）的人类NK细胞亚群的特征。这些NK细胞，我们称之为NK-22细胞，由急性暴露于IL-23触发。在体外，NK-22分泌的细胞因子刺激上皮细胞分泌IL-10，增殖并表达多种促有丝分裂和抗凋亡分子。NK-22细胞也存在于小鼠MALT中，并在细菌感染期间出现在小肠固有层中，表明NK-22细胞提供了IL-22的先天来源，这可能有助于抑制炎症并保护粘膜部位。
Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally-infected cells and tumor cells through release of cytolytic mediators and IFN-γ. In humans, blood CD56dim NK cells specialize in lysis of cell targets. In lymph nodes, CD56bright NK cells secrete IFN-γ cooperating with dendritic cells (DC) and T cells in the generation of adaptive responses. Here we report the characterization of a human NK cell subset located in mucosa-associated lymphoid tissues (MALT), such as tonsils and Payer’s patches, which is hard-wired to secrete interleukin (IL)-22, IL-26, and leukaemia inhibitory factor (LIF). These NK cells, which we refer to as NK-22 cells, are triggered by acute exposure to IL-23. In vitro, NK-22-secreted cytokines stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules. NK-22 cells are also found in mouse MALT and appear in the small intestine lamina propria during bacterial infection suggesting that NK-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites.
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