Immunoregulatory cytokine networks: 60 years of learning from murine cytomegalovirus.
Immunoregulatory cytokine networks: 60 years of learning from murine cytomegalovirus.
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DOI：
10.1007/s00430-015-0412-3
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发表时间：
2015-06
影响因子：
5.4
通讯作者：
Tarrio ML
中科院分区：
文献类型：
--
作者：
Biron CA;Tarrio ML
先天免疫防御感染，但也介导形成先天和适应性反应的免疫调节作用。小鼠巨细胞病毒（MCMV）感染的研究有助于阐明诱导机制，以及诱导的可溶性和细胞网络有助于先天免疫。特化受体通过感染诱导结构刺激关键先天细胞因子的产生。然后刺激细胞因子和细胞反应，如自然杀伤（NK）细胞的激活，介导1型干扰素（IFN）的升高杀伤和/或通过白细胞介素12 （IL-12）产生促炎和抗病毒的细胞因子IFN-γ。一个系统间循环，与IL-6诱导糖皮质激素释放，负调控这些早期细胞因子反应。然而，随着感染进入先天和适应性反应重叠的时期，细胞在本质上受到调节，以改变暴露于个体细胞因子的生物效应。一些通路被关闭以抑制现有的反应功能，而另一些通路被拓宽以获得新的反应功能。值得注意的是，MCMV感染期间NK细胞增殖的延长与表观遗传修饰有关，这些修饰将抑制性细胞因子IL-10基因的状态从关闭转变为打开，并导致它们具备产生该细胞因子的能力。当诱导时，NK细胞IL-10负性调节适应性反应的大小，以防止免疫病理。因此，先天免疫调节细胞因子网络是促炎和防御功能不可或缺的一部分，但响应细胞具有灵活性，可以通过改变网络特征进行细胞内在调节，从而产生新的负免疫调节功能，从而促进有益的免疫反应并限制有害的免疫反应。
Innate immunity defends against infection but also mediates immunoregulatory effects shaping innate and adaptive responses. Studies of murine cytomegalovirus (MCMV) infections have helped elucidate the mechanisms inducing, as well as the elicited soluble and cellular networks contributing to, innate immunity. Specialized receptors are engaged by infection-induced structures to stimulate production of key innate cytokines. These then stimulate cytokine and cellular responses such as activation of natural killer (NK) cells to mediate elevated killing by type 1 interferon (IFN) and/or to produce the pro-inflammatory and antiviral cytokine IFN-γ by interleukin 12 (IL-12). An inter-systemic loop, with IL-6 inducing glucocorticoid release, negatively regulates these early cytokine responses. As infections advance into periods of overlapping innate and adaptive responses, however, the cells are intrinsically conditioned to modify the biological effects of exposure to individual cytokines. Some pathways are turned off to inhibit an existing, whereas others are broadened for acquisition of a new, response function. Remarkably, extended NK cell proliferation during MCMV infection is associated with epigenetic modifications shifting the state of the inhibitory cytokine IL-10 gene from closed to open, and results in their becoming equipped to produce this cytokine. When induced, NK cell IL-10 negatively regulates the magnitude of adaptive responses to protect against immune pathology. Thus, innate immunoregulatory cytokine networks are integral to pro-inflammatory and defense functions, but responding cells have the flexibility to undergo cell intrinsic conditioning with changing network characteristics to result in a new negative immunoregulatory function and consequently, both promote beneficial and limit detrimental immune responses.
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DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Jonjic, Stipan;Polic, Bojan;Krmpotic, Astrid
通讯作者：
Krmpotic, Astrid
影响因子：
56.9
作者：
Brown, MG;Dokun, AO;Yokoyama, WM
通讯作者：
Yokoyama, WM
DOI：
10.4161/jkst.23504
发表时间：
2013-01-01
期刊：
JAK-STAT
影响因子：
--
作者：
Kallal LE;Biron CA
通讯作者：
Biron CA
影响因子：
5.4
作者：
De Maria, Andrea;Fogli, Manuela;Moretta, Lorenzo
通讯作者：
Moretta, Lorenzo