Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice
Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice
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DOI：
10.1084/jem.20181604
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发表时间：
2019-04-01
影响因子：
15.3
通讯作者：
Hase, Koji
中科院分区：
文献类型：
--
作者：
Kimura, Shunsuke;Kobayashi, Nobuhide;Hase, Koji
肠道相关淋巴组织的滤泡相关上皮（FAE）中的微折叠（M）细胞专门用于抗原摄取，以启动粘膜免疫应答。然而，M细胞分化的分子机制和生物学意义仍有待充分阐明。在这里，我们证明了Sox 8，SRY相关的HMG盒转录因子家族的成员，是由肠上皮中的M细胞特异性表达。Sox 8的表达需要RANKL-RelB信号传导的激活。染色质免疫沉淀和荧光素酶分析显示，Sox 8直接结合Gp 2的启动子区，以增加Gp 2的表达，这是功能成熟的M细胞的标志。此外，Sox 8基因缺失导致成熟M细胞数量显著减少，导致派尔集合淋巴结中抗原摄取减少。因此，幼年Sox 8缺陷小鼠表现出减弱的生发中心反应和抗原特异性伊加反应。这些发现表明Sox 8在M细胞的发育中起着重要作用，以建立粘膜免疫应答。
Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.