IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells.
IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells.
复制标题
DOI：
10.4049/jimmunol.0803721
复制
发表时间：
2009-09-01
期刊：
影响因子：
--
通讯作者：
Cooper KD
中科院分区：
文献类型：
--
作者：
Goodman WA;Levine AD;Massari JV;Sugiyama H;McCormick TS;Cooper KD
从银屑病患者中分离的T记忆/效应细胞（T细胞/效应细胞）被调节性T细胞（Treg）慢性激活且抑制不良。促炎细胞因子IL-6通过Stat 3发出信号，允许TcR/eff细胞从鼠系统中Treg介导的抑制中逃逸。我们在这里表明，IL-6蛋白显着升高，最高表达的CD 31+内皮细胞和CD 11 c+真皮树突状细胞（DC）在皮损银屑病皮肤。我们假设，暴露于高IL-6的病变组织可能会导致抑制Treg功能观察银屑病患者。事实上，我们发现，IL-6，而不是其他Stat 3激活细胞因子，是必要的和足够的逆转人T细胞抑制Treg在体外模型中使用活化的DC作为IL-6的来源。银屑病患者效应T细胞中IL-6 R α和gp 130的表达较正常对照组明显升高。总体而言，Treg上的IL-6 R α表达超过效应T细胞的表达，并且两个群体响应于IL-6而磷酸化Stat 3。T细胞中Stat 3的磷酸化有助于Th 17的分化，我们鉴定了共表达CD 3、IL-17和IL-6的皮损组织中的细胞，表明Th 17细胞存在于银屑病患者的TcR/eff群体中，并有助于IL-6介导的对Treg抑制的抵抗。总之，T淋巴细胞运输到银屑病皮损皮肤中遇到来自内皮细胞、DC和Th 17细胞的高IL-6，使得皮肤T细胞能够逃避Treg抑制和Th 17参与炎症。靶向银屑病中的IL-6信号通路可以重新平衡Treg/T效应子活性并改善疾病。
T memory/effector cells (Tmem/eff) isolated from psoriatic patients are chronically activated and poorly suppressed by regulatory T cells (Treg). The proinflammatory cytokine IL-6, which signals through Stat3, allows escape of Tmem/eff cells from Treg-mediated suppression in a murine system. We show here that IL-6 protein is markedly elevated and most highly expressed by CD31+ endothelial cells and CD11c+ dermal dendritic cells (DCs) in lesional psoriatic skin. We hypothesized that exposure to high IL-6 in lesional tissue may lead to the dampened Treg function observed in psoriasis patients. Indeed, we found that IL-6, but not other Stat3-activating cytokines, was necessary and sufficient to reverse human T cell suppression by Treg in an in vitro model using activated DCs as a source of IL-6. IL-6Rα and gp130 expression was significantly elevated in psoriatic effector T cells compared with normal controls. Overall, IL-6Rα expression on Treg exceeded that of effector T cells, and both populations phosphorylated Stat3 in response to IL-6. Phosphorylation of Stat3 in T cells contributes to Th17 differentiation and we identify cells within lesional tissue that coexpress CD3, IL-17, and IL-6, indicating that Th17 cells are present in vivo within the psoriatic Tmem/eff population and contribute to IL-6-mediated resistance to Treg suppression. Taken together, T lymphocytes trafficking into lesional psoriatic skin encounter high IL-6 from endothelial cells, DCs, and Th17 cells, enabling cutaneous T cell escape from Treg suppression and Th17 participation in inflammation. Targeting IL-6 signaling pathways in psoriasis may rebalance Treg/T effector activity and ameliorate disease.
登录
查看更多内容
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1073/pnas.0705268104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Kimura, Akihiro;Naka, Tetsuji;Kishimoto, Tadamitsu
通讯作者：
Kishimoto, Tadamitsu
影响因子：
6.5
作者：
COOPER, KD;BAADSGAARD, O;VOORHEES, JJ
通讯作者：
VOORHEES, JJ
影响因子：
6.5
作者：
NEUNER, P;URBANSKI, A;LUGER, TA
通讯作者：
LUGER, TA
DOI：
10.1073/pnas.86.16.6367
发表时间：
1989-08-01
影响因子：
11.1
作者：
GROSSMAN, RM;KRUEGER, J;GOTTLIEB, AB
通讯作者：
GOTTLIEB, AB