Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells
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DOI：
10.1038/nature08636
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发表时间：
2010-01-28
期刊：
影响因子：
64.8
通讯作者：
Koyasu, Shigeo
中科院分区：
文献类型：
--
作者：
Moro, Kazuyo;Yamada, Taketo;Koyasu, Shigeo
在感染的早期阶段，先天免疫反应在对抗各种微生物方面是重要的。自然杀伤细胞（NK）是先天淋巴细胞，与T淋巴细胞和B淋巴细胞不同，NK细胞不表达抗原受体，但对病毒感染的细胞迅速表现出细胞毒活性，并产生各种细胞因子（1,2）。在这里，我们报告了一种新的先天淋巴细胞存在于与腹腔脂肪组织相关的新型淋巴样结构中。这些细胞不表达谱系（Lin）标记，但表达c-Kit、Sca-1（也称为Ly6a）、IL7R和IL33R。在人和小鼠肠系膜中都发现了类似的淋巴细胞簇，我们将这种组织称为“FALC”（脂肪相关淋巴细胞簇）。FALC Lin(-)c-Kit(+)Sca-1（+）细胞不同于淋巴样祖细胞(3)和淋巴样组织诱导细胞(4)。这些细胞在IL2的作用下增殖，并产生大量的T(H)2细胞因子，如IL5、IL6和IL13。IL5和IL6调节b细胞抗体的产生和B1细胞的自我更新（5-7）。事实上，FALC Lin(-)c-Kit(+)Sca-1（+）细胞支持B1细胞的自我更新并增强IgA的产生。IL5和IL13介导过敏性炎症和对蠕虫感染的保护（8,9）。在蠕虫感染后，作为对IL33的反应，FALC Lin(-)c-Kit(+)Sca-1（+）细胞产生大量的IL13，从而导致杯状细胞增生——这是驱逐蠕虫的关键步骤。在缺乏FALC Lin(-)c-Kit(+)Sca-1（+）细胞的小鼠中，不诱导这种杯状细胞增生。因此，FALC Lin(-)c-Kit(+)Sca-1（+）细胞是T(H)2型先天淋巴细胞，我们建议将这些细胞称为“天然辅助细胞”。
Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines(1,2). Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors(3) and lymphoid tissue inducer cells(4). These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells(5-7). Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection(8,9). After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.