IL-27 receptor signaling regulates CD4+ T cell chemotactic responses during infection.
IL-27 receptor signaling regulates CD4+ T cell chemotactic responses during infection.
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DOI：
10.4049/jimmunol.1202916
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发表时间：
2013-05-01
期刊：
影响因子：
--
通讯作者：
Couper KN
中科院分区：
文献类型：
--
作者：
Gwyer Findlay E;Villegas-Mendez A;de Souza JB;Inkson CA;Shaw TN;Saris CJ;Hunter CA;Riley EM;Couper KN
IL-27在感染和炎症期间对初始和效应T细胞群发挥多效性抑制作用。然而，令人惊讶的是，IL-27在限制或塑造效应CD 4 + T细胞趋化反应中的作用，作为减少T细胞依赖性组织炎症的机制，是未知的。在这项研究中，使用伯氏疟原虫NK 65作为一个系统性的，促炎性感染的模型，我们证明，IL-27 R信号抑制感染源性脾CD 4 + T细胞的趋化性响应CCR 5配体，CCL 4和CCL 5。与这些观察结果一致，与感染的野生型（WT）小鼠相比，在疟疾感染的IL-27 R缺陷（WSX-1−/−）小鼠的脾脏CD 4 + T细胞上，CCR 5的表达频率显著更高。我们发现，IL-27信号抑制脾CD 4 + T细胞CCR 5依赖性趋化反应在感染过程中，通过限制CCR 5表达的CD 4 + T细胞亚型，包括Th 1细胞，也通过控制的整体组成的CD 4 + T细胞室。通过中和IL-12 p40，体内感染WSX-1−/−小鼠的Th 1应答减弱，感染源性CD 4 + T细胞的CCR 5表达减弱，也降低了脾脏CD 4 + T细胞对CCL 4和CCL 5的趋化性。这些数据揭示了IL-27在感染过程中调节CD 4 + T细胞趋化途径的作用，这与其抑制Th 1效应细胞发育的能力有关。因此，IL-27似乎是在炎症环境中限制CCR 5-CCL 4/CCL 5轴的关键细胞因子。
IL-27 exerts pleiotropic suppressive effects on naïve and effector T cell populations during infection and inflammation. Surprisingly, however, the role of IL-27 in restricting or shaping effector CD4+ T cell chemotactic responses, as a mechanism to reduce T cell-dependent tissue inflammation, is unknown. In this study, using Plasmodium berghei NK65 as a model of a systemic, pro-inflammatory infection, we demonstrate that IL-27R signalling represses chemotaxis of infection-derived splenic CD4+ T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4+ T cells from malaria-infected, IL-27R deficient (WSX-1−/−) mice than from infected wild type (WT) mice. We find that IL-27 signalling suppresses splenic CD4+ T cell CCR5-dependent chemotactic responses during infection by restricting CCR5 expression on CD4+ T cell sub-types, including Th1 cells, and also by controlling the overall composition of the CD4+ T cell compartment. Diminution of the Th1 response in infected WSX-1−/− mice in vivo by neutralisation of IL-12p40 attenuated CCR5 expression by infection-derived CD4+ T cells and also reduced splenic CD4+ T cell chemotaxis towards CCL4 and CCL5. These data reveal a previously unappreciated role for IL-27 in modulating CD4+ T cell chemotactic pathways during infection, which is related to its capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings.
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影响因子：
4.4
作者：
Diveu, Caroline;McGeachy, Mandy J.;Kastelein, Robert A.
通讯作者：
Kastelein, Robert A.
影响因子：
32.4
作者：
Hamano, S;Himeno, K;Yoshida, H
通讯作者：
Yoshida, H
DOI：
10.1073/pnas.2536517100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Lucas, S;Ghilardi, N;de Sauvage, FJ
通讯作者：
de Sauvage, FJ
影响因子：
4.4
作者：
Iwasaki, M;Mukai, T;Hamaoka, T
通讯作者：
Hamaoka, T
影响因子：
4.4
作者：
Artis, D;Villarino, A;Hunter, CA
通讯作者：
Hunter, CA