Cellular context of IL-33 expression dictates impact on anti-helminth immunity.
Cellular context of IL-33 expression dictates impact on anti-helminth immunity.
复制标题
白细胞介素 - 33表达的细胞环境决定了其对抗蠕虫免疫的影响。
DOI：
10.1126/sciimmunol.abc6259
复制
发表时间：
2020-11-13
影响因子：
24.8
通讯作者：
Herbert DR
中科院分区：
文献类型：
--
作者：
Hung LY;Tanaka Y;Herbine K;Pastore C;Singh B;Ferguson A;Vora N;Douglas B;Zullo K;Behrens EM;Li Hui Tan T;Kohanski MA;Bryce P;Lin C;Kambayashi T;Reed DR;Brown BL;Cohen NA;Herbert DR
白介素33(IL-33)是一种多效性细胞因子，可以促进II型炎症，但也可以通过Foxp3+Treg的扩增来驱动免疫调节。目前尚不清楚IL-33是如何从细胞中输出，从而在免疫抑制和炎症中发挥双重作用的。在这里，我们证明了IL-33活性的生物学后果是由其细胞来源决定的。当来源于上皮细胞的IL-33刺激ILC2驱动的2型免疫和寄生虫清除时，我们报道来源于髓系抗原提呈细胞(APC)的IL-33抑制宿主保护性炎症反应。在表达CD11c的细胞中条件性缺失IL-33导致表达转录因子GATA3和IL-33受体ST2的肠道Foxp3+Treg细胞数量减少，导致IL-5和IL-13的产生增加，并加速抗蠕虫免疫。我们证明了细胞内源性IL-33促进小鼠DC表达穿孔素-2，穿孔素-2可能作为细胞膜上的管道促进IL-33输出。DC中缺乏穿孔素-2抑制了ST2+Foxp3+Treg亚群的增殖。我们认为，穿孔素-2可以在DC中提供一个质膜管道，促进IL-33的输出，在稳态和感染条件下有助于粘膜免疫调节。穿孔蛋白-2促进树突状细胞释放IL-33。
Interleukin-33 (IL-33) is a pleiotropic cytokine that can promote Type 2 inflammation, but also drives immunoregulation through Foxp3+ Treg expansion. How IL-33 is exported from cells to serve this dual role in immunosuppression and inflammation remains unclear. Here, we demonstrate that the biological consequences of IL-33 activity are dictated by its cellular source. While IL-33 derived from epithelial cells stimulates ILC2-driven Type 2 immunity and parasite clearance, we report that IL-33 derived from myeloid antigen-presenting cells (APC) suppresses host-protective inflammatory responses. Conditional deletion of IL-33 in CD11c-expressing cells resulted in lowered numbers of intestinal Foxp3+ Treg cells that express the transcription factor GATA3 and the IL-33 receptor ST2, causing elevated IL-5 and IL-13 production and accelerated anti-helminth immunity. We demonstrate that cell-intrinsic IL-33 promoted mouse DCs to express the pore-forming protein perforin-2, which may function as a conduit on the plasma membrane facilitating IL-33 export. Lack of perforin-2 in DCs blocked the proliferative expansion of the ST2+Foxp3+ Treg subset. We propose that perforin-2 can provide a plasma membrane conduit in DCs that promotes the export of IL-33 contributing to mucosal immunoregulation under steady-state and infectious conditions. The pore-forming protein perforin-2 facilitates IL-33 release from dendritic cells.
登录
查看更多内容
影响因子：
4.1
作者：
Boita M;Bucca C;Riva G;Heffler E;Rolla G
通讯作者：
Rolla G
DOI：
10.4049/jimmunol.1201224
发表时间：
2012-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hsu CL;Bryce PJ
通讯作者：
Bryce PJ
形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA