Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice
Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice
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DOI：
10.4049/jimmunol.172.5.2827
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
de Sauvage, FJ
中科院分区：
文献类型：
--
作者：
Ghilardi, N;Kljavin, N;de Sauvage, FJ
异二聚体细胞因子白细胞介素 - 23（IL - 23）由独特的类细胞因子p19亚基和类细胞因子受体亚基p40组成，p40与白细胞介素 - 12（IL - 12）共用。先前报道的白细胞介素 - 12p40缺陷型小鼠因白细胞介素 - 12和白细胞介素 - 23两者均缺乏而存在严重的免疫缺陷。为了探究特异性白细胞介素 - 23缺乏的影响，我们通过基因打靶技术培育了缺失p19的小鼠。这些小鼠没有明显的异常，但T细胞依赖性体液免疫应答严重受损。白细胞介素 - 23p19（ - / - ）小鼠产生的所有同种型的抗原特异性免疫球蛋白（Igs）水平大幅降低，但T细胞非依赖性B细胞应答正常。此外，在缺乏白细胞介素 - 23的情况下，迟发型超敏反应严重受损，这表明显记忆性T细胞水平存在缺陷。用白细胞介素 - 23缺陷型抗原提呈细胞（APCs）刺激的T细胞分泌的促炎细胞因子白细胞介素 - 17的量显著减少，并且白细胞介素 - 23缺陷型小鼠在表型上与白细胞介素 - 17缺陷型动物相似。因此，白细胞介素 - 23在T细胞依赖性免疫应答中起关键作用，我们的数据进一步支持了免疫系统适应性和先天性部分之间存在白细胞介素 - 23 / 白细胞介素 - 17通讯轴这一观点。
The heterodimeric cytokine IL-23 consists of a private cytokine-like p19 subunit and a cytokine receptor-like subunit, p40, which is shared with IL-12. Previously reported IL-12p40-deficient mice have profound immune defects resulting from combined deficiency in both IL-12 and IL-23. To address the effects of specific IL-23 deficiency, we generated mice lacking p19 by gene targeting. These mice display no overt abnormalities but mount severely compromised T-dependent humoral immune responses. IL-23p19(-/-) mice produce strongly reduced levels of Ag-specific Igs of all isotypes, but mount normal T-independent B cell responses. In addition, delayed type hypersensitivity responses are strongly impaired in the absence of IL-23, indicating a defect at the level of memory T cells. T cells stimulated with IL-23-deficient APCs secrete significantly reduced amounts of the proinflammatory cytokine IL-17, and IL-23-deficient mice phenotypically resemble IL-17-deficient animals. Thus, IL-23 plays a critical role in T cell-dependent immune responses, and our data provide further support for the existence of an IL-23/IL-17 axis of communication between the adaptive and innate parts of the immune system.