Seeking balance: Potentiation and inhibition of multiple sclerosis autoimmune responses by IL-6 and IL-10.
Seeking balance: Potentiation and inhibition of multiple sclerosis autoimmune responses by IL-6 and IL-10.
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DOI：
10.1016/j.cyto.2015.01.009
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发表时间：
2015-06
期刊：
影响因子：
3.8
通讯作者：
Davis, Laurie S.
中科院分区：
文献类型：
--
作者：
Ireland, Sara J.;Monson, Nancy L.;Davis, Laurie S.
细胞因子IL-6和IL-10由免疫系统的适应性和先天性臂的细胞产生，并且它们似乎在遗传多样性自身免疫性疾病如复发缓解型多发性硬化症（MS）、类风湿性关节炎（RA）和系统性红斑狼疮（SLE）中起关键作用。虽然以前的研究集中在自身抗体的产生及其对这些疾病中免疫介导的发病机制的贡献，但最近的注意力集中在细胞因子如IL-6和IL-10的作用上。在对病原体的应答中，抗原呈递细胞（APC），包括B细胞，产生IL-6和IL-10以上调或下调免疫细胞活化和效应子应答。在炎症反应期间和许多自身免疫性疾病中常规观察到促炎细胞因子IL-6水平升高的证据。我们最近的研究表明，MS外周血B细胞分泌的IL-6和IL-10比健康对照组的B细胞更高的数量和更少。IL-6的持续产生反过来有助于T细胞扩增和APC如MS B细胞的功能性过度活跃。改变的B细胞活性可对所得T细胞效应子功能具有深远影响。通过IL-6受体增强的信号传导可以有效地抑制细胞溶解活性，诱导T细胞对IL-10介导的免疫抑制的抗性，并增加自身反应性T细胞向致病性Th 17表型的偏斜。我们最近的发现和其他人的研究支持醋酸格拉替雷（GA）治疗间接减弱B细胞应答的作用。我们的研究表明，GA治疗暂时允许恢复稳态调节机制。未来对B细胞细胞因子产生失调的机制的研究可能会导致识别新的靶点，以改善自身免疫性疾病的免疫调节疗法。
The cytokines IL-6 and IL-10 are produced by cells of the adaptive and innate arms of the immune system and they appear to play key roles in genetically diverse autoimmune diseases such as relapsing remitting multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Whereas previous intense investigations focused on the generation of autoantibodies and their contribution to immune-mediated pathogenesis in these diseases more recent attention has focused on the roles of cytokines such as IL-6 and IL-10. In response to pathogens, antigen presenting cells (APC), including B cells, produce IL-6 and IL-10 in order to up- or down-regulate immune cell activation and effector responses. Evidence of elevated levels of the proinflammatory cytokine IL-6 has been routinely observed during inflammatory responses and in a number of autoimmune diseases. Our recent studies suggest that MS peripheral blood B cells secrete higher quantities of IL-6 and less IL-10 than B cells from healthy controls. Persistent production of IL-6, in turn, contributes to T cell expansion and the functional hyperactivity of APC such as MS B cells. Altered B cell activity can have a profound impact on resultant T cell effector functions. Enhanced signaling through the IL-6 receptor can effectively inhibit cytolytic activity, induce T cell resistance to IL-10-mediated immunosuppression and increase skewing of autoreactive T cells to a pathogenic Th17 phenotype. Our recent findings and studies by others support a role for the indirect attenuation of B cell responses by Glatiramer acetate (GA) therapy. Our studies suggest that GA therapy temporarily permits homeostatic regulatory mechanisms to be reinstated. Future studies of mechanisms underlying dysregulated B cell cytokine production could lead to the identification of novel targets for improved immunoregulatory therapies for autoimmune diseases.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.94.20.10821
发表时间：
1997-09-30
影响因子：
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作者：
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通讯作者：
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DOI：
10.1084/jem.20111675
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
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