Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo.
Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo.
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DOI：
10.4049/jimmunol.0902408
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发表时间：
2010-01-15
期刊：
影响因子：
--
通讯作者：
Mohrs M
中科院分区：
文献类型：
--
作者：
Perona-Wright G;Mohrs K;Mayer KD;Mohrs M
IL-4促进Th2分化，提供对蠕虫感染的免疫力，但也与过敏和哮喘有关。这表明，要正确平衡免疫反应，需要精确调节IL-4的反应性。IL-4Rα链是IL-4受体的重要组成部分，通过STAT6传递信号。在这项研究中，我们发现感染了蠕虫病原体后，引流淋巴结旁的CD_4~+T细胞上IL-4Rα大量上调，同时导致活化的Th2细胞上IL-4Rα的表达缺失。IL-4Rα上调仅限于反应性淋巴结，在感染后4d内发生，并受IL-4和STAT6依赖的机制驱动。STAT6杂合子的小鼠表现出IL-4Rα上调减少，Th2型反应相应减弱。事实上，与C57BL6小鼠相比，BALB/c小鼠IL-4Rα上调预示着它们更强的Th2反应。IL-4Rα在高活化的Th细胞上的选择性下调是由抗原刺激触发的，伴随着IL-7Rα的丢失，使细胞对IL-4无反应。总而言之，这些数据揭示了一个严格控制的改变IL-4反应的程序，该程序表征了体内Th2反应的启动、放大和限制。
IL-4 promotes Th2 differentiation and provides immunity to helminth infections but is also associated with allergy and asthma. This suggests that precise adjustment of IL-4 responsiveness is needed to correctly balance immune responses. The IL-4Rα chain is an essential component of the IL-4 receptor and signals via STAT6. In this study, we show that infection with a helminth pathogen elicited broad upregulation of IL-4Rα on bystander CD4+ T cells in the draining lymph node, while simultaneously resulting in the loss of IL-4Rα expression on activated Th2 cells. IL-4Rα upregulation was restricted to the reactive lymph node, occurred within 4 d of infection, and was driven by an IL-4– and STAT6–dependent mechanism. Mice heterozygous for Stat6 exhibited reduced IL-4Rα upregulation and a correspondingly attenuated Th2 response. Indeed, the enhanced IL-4Rα upregulation in BALB/c mice, compared with that in C57BL6 mice, predicted their stronger Th2 response. The selective downregulation of IL-4Rα on highly activated Th cells was triggered by antigenic stimulation, was accompanied by loss of IL-7Rα, and rendered the cells unresponsive to IL-4. Together these data reveal a tightly controlled program of changing IL-4 responsiveness that characterizes the initiation, amplification, and restriction of a Th2 response in vivo.
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DOI：
10.1073/pnas.83.24.9689
发表时间：
1986-12-01
影响因子：
11.1
作者：
FERNANDEZBOTRAN, R;SANDERS, VM;VITETTA, ES
通讯作者：
VITETTA, ES
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
32.4
作者：
Grogan, JL;Mohrs, M;Locksley, RM
通讯作者：
Locksley, RM
影响因子：
4.4
作者：
Eisenbarth, SC;Zhadkevich, A;Bottomly, K
通讯作者：
Bottomly, K
DOI：
10.1084/jem.20062381
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dooms H;Wolslegel K;Lin P;Abbas AK
通讯作者：
Abbas AK