Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity
Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity
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DOI：
10.1073/pnas.1005641107
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发表时间：
2010-06-15
影响因子：
11.1
通讯作者：
Colonna, Marco
中科院分区：
文献类型：
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作者：
Cella, Marina;Otero, Karel;Colonna, Marco
自然杀伤-22 （NK-22）细胞是位于粘膜相关淋巴组织中的人类NK细胞亚群，专门分泌IL-22以响应IL-23。在这里，我们研究NK-22细胞扩增所需的细胞因子。IL-7维持NK-22细胞的存活和IL-22的产生以响应IL-23，但不足以诱导稳健的增殖。在IL-7中加入IL-1 β或IL-2均能显著促进NK-22细胞的增殖，且在IL-1 β + IL-2的情况下增殖更强。与IL-7相比，IL-1 β和IL-2的连续培养改变了NK-22细胞因子的谱。在一些细胞中，IL-1 β促进构成性IL-22分泌，而不是响应IL-23的急性IL-22分泌，并诱导IL-17。IL-2降低IL-22和IL-17的分泌，增加ifn - γ和白血病抑制因子的产生。IL-23的连续培养也诱导了ifn - γ产生的功能偏差。这些结果表明NK-22细胞的功能可塑性，这可能允许灵活的反应不同的病原体。最后，我们发现NK-22细胞释放b细胞存活因子，b细胞活化因子属于TNF家族（BAFF），提示NK-22细胞在促进b细胞介导的粘膜免疫中可能发挥作用。
Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the survival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1 beta or IL-2 to IL-7 and was even stronger in the presence of IL-1 beta plus IL-2. In contrast to IL-7, continuous culture in IL-1 beta and IL-2 modified NK-22 cytokine profiles. IL-1 beta promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-gamma and leukemia inhibitory factor. Functional deviation toward IFN-gamma production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell-mediated mucosal immunity.