Interleukin-36γ is expressed by neutrophils and can activate microglia, but has no role in experimental autoimmune encephalomyelitis.
Interleukin-36γ is expressed by neutrophils and can activate microglia, but has no role in experimental autoimmune encephalomyelitis.
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DOI：
10.1186/s12974-015-0392-7
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发表时间：
2015-09-17
影响因子：
9.3
通讯作者：
Vallières L
中科院分区：
文献类型：
--
作者：
Bozoyan L;Dumas A;Patenaude A;Vallières L
实验性自身免疫性脑脊髓炎（EAE）是一种由不同类型白细胞介导的炎症性脱髓鞘疾病模型。这些细胞如何相互沟通以协同进行自身免疫攻击尚未完全了解，特别是在中性粒细胞方面，其在EAE中的重要性是新近确立的。本研究旨在确定白细胞介素 - 36信号通路（IL - 36α、IL - 36β、IL - 36γ、IL - 36R）的不同成分在EAE中的表达模式和作用。
通过用髓鞘肽主动免疫、髓鞘反应性T细胞被动转移或向转基因2D2小鼠注射百日咳毒素诱导EAE。使用多种技术组合分析感兴趣的分子，包括定量实时聚合酶链反应（qRT - PCR）、流式细胞术、蛋白质印迹法、原位杂交和免疫组织化学。用重组IL - 36γ处理小胶质细胞培养物，并使用DNA微阵列进行分析。对不同小鼠品系进行临床评估和流式细胞术分析，以比较它们对EAE的易感性。
我们的观察结果表明，在不同形式的EAE中，IL - 36γ和IL - 36R在神经和造血组织中均强烈上调。IL - 36γ由中性粒细胞特异性表达，而IL - 36R由不同的免疫细胞表达，包括小胶质细胞和其他髓系细胞。在培养中，小胶质细胞通过表达参与中性粒细胞募集的分子（如Csf3、IL - 1β和Cxcl2）对重组IL - 36γ作出反应。然而，与野生型对照相比，IL - 36γ或IL - 36R缺陷的小鼠出现相似的EAE临床和组织病理学症状。
这项研究将IL - 36γ确定为一种与中性粒细胞相关的细胞因子，它可能激活小胶质细胞，但在EAE中仅具有相关性而非致病性。
本文的在线版本（doi:10.1186/s12974 - 015 - 0392 - 7）包含补充材料，授权用户可获取。
Experimental autoimmune encephalomyelitis (EAE) is a model of inflammatory demyelinating diseases mediated by different types of leukocytes. How these cells communicate with each other to orchestrate autoimmune attacks is not fully understood, especially in the case of neutrophils, whose importance in EAE is newly established. The present study aimed to determine the expression pattern and role of different components of the IL-36 signaling pathway (IL-36α, IL-36β, IL-36γ, IL-36R) in EAE. EAE was induced by either active immunization with myelin peptide, passive transfer of myelin-reactive T cells or injection of pertussis toxin to transgenic 2D2 mice. The molecules of interest were analyzed using a combination of techniques, including quantitative real-time PCR (qRT-PCR), flow cytometry, Western blotting, in situ hybridization, and immunohistochemistry. Microglial cultures were treated with recombinant IL-36γ and analyzed using DNA microarrays. Different mouse strains were subjected to clinical evaluation and flow cytometric analysis in order to compare their susceptibility to EAE. Our observations indicate that both IL-36γ and IL-36R are strongly upregulated in nervous and hematopoietic tissues in different forms of EAE. IL-36γ is specifically expressed by neutrophils, while IL-36R is expressed by different immune cells, including microglia and other myeloid cells. In culture, microglia respond to recombinant IL-36γ by expressing molecules involved in neutrophil recruitment, such as Csf3, IL-1β, and Cxcl2. However, mice deficient in either IL-36γ or IL-36R develop similar clinical and histopathological signs of EAE compared to wild-type controls. This study identifies IL-36γ as a neutrophil-related cytokine that can potentially activate microglia, but that is only correlative and not contributory in EAE. The online version of this article (doi:10.1186/s12974-015-0392-7) contains supplementary material, which is available to authorized users.