IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression.
IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression.
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作者：
白细胞介素 (IL)-12 已被证明可以抑制 2 型辅助性 T (Th2) 诱导的与过敏性哮喘相关的发病机制，主要是通过干扰素 (IFN)-γ 的产生。我们最近发现，在缺乏 IFN-γ 表达的主要调节因子 T-bet 的情况下，过敏性肺部炎症主要与 IL-17 相关的中性粒细胞募集到小鼠肺道有关。在没有 T-bet 的情况下，外源性 IL-12 仍然能够抑制中性粒细胞浸润，并降低 IL-17、IL-23 和 IL-23R 以及视黄酸相关孤儿受体γt（Th17 途径的转录调节因子）的水平。在 T-bet−/− IFN-γ−/− 双敲除小鼠中观察到了相同的效果，表明在该模型中 IL-12 具有不依赖于 IFN-γ 的作用。 IL-12 治疗后，T-bet 缺陷小鼠肺部的 IL-10 表达显着增加，并且接种抗 IL-10R mAb 完全逆转了 IL-12 抑制组织学炎症、炎症细胞亚群募集到肺部、细支气管高反应性和 IL-17 产生的能力。我们的结论是，在缺乏有效的 IFN-γ 信号传导的情况下，Th17 介导的过敏性肺部炎症占主导地位，IL-12 可以通过 IL-10 依赖性机制有效抑制这种炎症。
Interleukin (IL)-12 has been shown to suppress T helper type 2 (Th2)-induced pathogenesis that is associated with allergic asthma, largely through interferon (IFN)-γ production. We have recently shown that in the absence of T-bet, the major regulator of IFN-γ expression, allergic lung inflammation is primarily associated with IL-17-associated recruitment of neutrophils into the pulmonary tract of mice. In the absence of T-bet, exogenous IL-12 was still able to suppress neutrophilic infiltration and to diminish levels of IL-17, IL-23, and IL-23R, as well as retinoic acid-related orphan receptorγt, the transcriptional regulator of the Th17 pathway. The same effects were observed in T-bet−/− IFN-γ−/− double knockout mice, showing an IFN-γ-independent effect of IL-12 in this model. IL-10 expression in the lungs of T-bet-deficient mice was significantly increased after IL-12 treatment, and inoculation of anti-IL-10R mAb completely reversed the ability of IL-12 to suppress histological inflammation, recruitment of inflammatory cell subsets into the lung, bronchiole hyperresponsiveness, and IL-17 production. We conclude that Th17-mediated allergic lung inflammation that becomes dominant in the absence of effective IFN-γ signaling can be effectively suppressed by IL-12 through an IL-10-dependent mechanism.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
5.4
作者：
Gu, Yongpeng;Yang, Jianfei;Ouyang, Xinshou;Liu, Weicheng;Li, Hongxing;Yang, Jianjun;Bromberg, Jonathan;Chen, Shu-Hsia;Mayer, Lloyd;Unkeless, Jay C.;Xiong, Huabao
通讯作者：
Xiong, Huabao
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
32.4
作者：
Jankovic, D;Kullberg, MC;Sher, A
通讯作者：
Sher, A
影响因子：
4.4
作者：
Henry, Emmanuelle;Desmet, Christophe J.;Bureau, Fabrice
通讯作者：
Bureau, Fabrice