Maternal IL-17A in autism.
Maternal IL-17A in autism.
复制标题
DOI：
10.1016/j.expneurol.2017.04.010
复制
发表时间：
2018-01
影响因子：
5.3
通讯作者：
Hoeffer C
中科院分区：
文献类型：
--
作者：
Wong H;Hoeffer C
虽然自闭症谱系障碍（ASD）具有很强的遗传基础，但其病因复杂，可能涉及多种遗传因素以及环境因素。免疫失调作为ASD发病机制的一种病因机制已经引起了广泛的关注。ASD与大脑和外周的免疫异常有关，包括受影响个体及其母亲的炎症性疾病和自身免疫。产前暴露于母体免疫激活（MIA）已被认为是ASD的环境危险因素。为了支持这一观点，动物模型表明MIA会导致后代出现与ASD相似的行为、神经和免疫异常。这就提出了一个问题：MIA暴露是如何在易感个体中导致ASD的。最近的证据表明，mia相关性ASD与T辅助性17 （Th17）淋巴细胞及其效应细胞因子白细胞介素- 17a （IL-17A）的活性之间存在潜在的炎症途径。IL-17A与人类研究有关，并且在一部分ASD个体中发现血液中IL-17A水平升高与表型严重程度相关。在MIA模型小鼠中，也观察到IL-17A水平升高。此外，发现抑制IL-17A信号的抗体阻断可以阻止暴露于MIA的后代的asd样行为。因此，IL-17A失调可能在ASD的发展中起因果作用。MIA小鼠模型中IL-17A增加的来源归因于母体Th17细胞，因为遗传去除转录因子RORγt以选择性地抑制妊娠小鼠Th17分化能够阻止后代的asd样行为。与ASD个体相似，暴露于mia的后代也表现出皮质发育不良，这可以通过抑制怀孕小鼠的IL-17A信号传导来预防。这一发现揭示了一种可能的细胞机制，通过这种机制，asd相关的认知和行为缺陷可能在母体炎症后出现。IL-17A可以对细胞存活和分化以及信号转导级联的活性产生强烈影响，从而在皮层发育过程中对神经功能产生重要影响。本文综述了IL-17A信号通路在免疫和神经功能的背景下可能有助于MIA相关ASD的发展。
Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental factors. Immune dysregulation has gained significant attention as a causal mechanism in ASD pathogenesis. ASD has been associated with immune abnormalities in the brain and periphery, including inflammatory disorders and autoimmunity in not only the affected individuals but also their mothers. Prenatal exposure to maternal immune activation (MIA) has been implicated as an environmental risk factor for ASD. In support of this notion, animal models have shown that MIA results in offspring with behavioral, neurological, and immunological abnormalities similar to those observed in ASD. This raises the question of how MIA exposure can lead to ASD in susceptible individuals. Recent evidence points to a potential inflammation pathway linking MIA-associated ASD with the activity of T helper 17 (Th17) lymphocytes and their effector cytokine interleukin-17A (IL-17A). IL-17A has been implicated from human studies and elevated IL-17A levels in the blood have been found to correlate with phenotypic severity in a subset of ASD individuals. In MIA model mice, elevated IL-17A levels also have been observed. Additionally, antibody blockade to inhibit IL-17A signaling was found to prevent ASD-like behaviors in offspring exposed to MIA. Therefore, IL-17A dysregulation may play a causal role in the development of ASD. The source of increased IL-17A in the MIA mouse model was attributed to maternal Th17 cells because genetic removal of the transcription factor RORγt to selectively inhibit Th17 differentiation in pregnant mice was able to prevent ASD-like behaviors in the offspring. Similar to ASD individuals, the MIA-exposed offspring also displayed cortical dysplasia which could be prevented by inhibition of IL-17A signaling in pregnant mice. This finding reveals one possible cellular mechanism through which ASD-related cognitive and behavioral deficits may emerge following maternal inflammation. IL-17A can exert strong effects on cell survival and differentiation and the activity of signal transduction cascades, which can have important consequences during cortical development on neural function. This review examines IL-17A signaling pathways in the context of both immunity and neural function that may contribute to the development of ASD associated with MIA.
登录
查看更多内容
影响因子：
3.3
作者：
Akintunde, Marjannie Eloi;Rose, Melissa;de Water, Judy Van
通讯作者：
de Water, Judy Van
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：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA