Memory-type ST2(+)CD4(+) T cells participate in the steroid-resistant pathology of eosinophilic pneumonia.
Memory-type ST2(+)CD4(+) T cells participate in the steroid-resistant pathology of eosinophilic pneumonia.
复制标题
DOI：
10.1038/s41598-017-06962-x
复制
发表时间：
2017-07-28
影响因子：
4.6
通讯作者：
Nakayama T
中科院分区：
文献类型：
--
作者：
Mato N;Hirahara K;Ichikawa T;Kumagai J;Nakayama M;Yamasawa H;Bando M;Hagiwara K;Sugiyama Y;Nakayama T
肺形成了独特的上皮屏障系统，以保护宿主免受各种有害颗粒的持续入侵。从肺上皮细胞释放的白细胞介素（IL-）33通过激活各种过敏性疾病中表达ST 2的免疫细胞来驱动2型免疫应答。然而，记忆型ST 2 + CD 4 + T细胞参与这种肺部炎症仍不清楚。在这里，我们证明了IL-33的气管内给药导致肺中组织驻留记忆型ST 2 + CD 4 + T细胞数量的大幅增加。随着IL-5和IL-13的产生增加，嗜酸性粒细胞性肺部炎症依次发展。IL-33介导的嗜酸性粒细胞性肺部炎症在T细胞缺陷型Foxn 1 nu小鼠和NSG小鼠中没有完全发展。地塞米松治疗对记忆型ST 2 + CD 4 + T细胞的细胞数量和功能的影响有限。因此，我们的研究提供了新的见解嗜酸性粒细胞性肺病的发病机制，显示记忆型ST 2 + CD 4 + T细胞参与IL-33诱导的嗜酸性粒细胞炎症和引起类固醇耐药性。
The lung develops an unique epithelial barrier system to protect host from continuous invasion of various harmful particles. Interleukin (IL-)33 released from epithelial cells in the lung drives the type 2 immune response by activating ST2− expressed immune cells in various allergic diseases. However, the involvement of memory-type ST2+CD4+ T cells in such lung inflammation remains unclear. Here we demonstrated that intratracheal administration of IL-33 resulted in the substantial increase of numbers of tissue-resident memory-type ST2+CD4+ T cells in the lung. Following enhanced production of IL-5 and IL-13, eosinophilic lung inflammation sequentially developed. IL-33-mediated eosinophilic lung inflammation was not fully developed in T cell-deficient Foxn1 nu mice and NSG mice. Dexamethasone treatment showed limited effects on both the cell number and function of memory-type ST2+CD4+ T cells. Thus our study provides novel insight into the pathogenesis of eosinophilic lung disease, showing that memory-type ST2+CD4+ T cells are involved in IL-33-induced eosinophilic inflammation and elicited steroid-resistance.
登录
查看更多内容
DOI：
10.4049/jimmunol.1501531
发表时间：
2016-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Manni ML;Mandalapu S;McHugh KJ;Elloso MM;Dudas PL;Alcorn JF
通讯作者：
Alcorn JF
影响因子：
32.4
作者：
Morita H;Arae K;Unno H;Miyauchi K;Toyama S;Nambu A;Oboki K;Ohno T;Motomura K;Matsuda A;Yamaguchi S;Narushima S;Kajiwara N;Iikura M;Suto H;McKenzie AN;Takahashi T;Karasuyama H;Okumura K;Azuma M;Moro K;Akdis CA;Galli SJ;Koyasu S;Kubo M;Sudo K;Saito H;Matsumoto K;Nakae S
通讯作者：
Nakae S
影响因子：
158.5
作者：
ALLEN, JN;PACHT, ER;DAVIS, WB
通讯作者：
DAVIS, WB
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
64.8
作者：
通讯作者：
--