Expression of IL-1β in rhesus EAE and MS lesions is mainly induced in the CNS itself.
Expression of IL-1β in rhesus EAE and MS lesions is mainly induced in the CNS itself.
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DOI：
10.1186/s12974-016-0605-8
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发表时间：
2016-06-06
影响因子：
9.3
通讯作者：
Bajramovic JJ
中科院分区：
文献类型：
--
作者：
Burm SM;Peferoen LA;Zuiderwijk-Sick EA;Haanstra KG;'t Hart BA;van der Valk P;Amor S;Bauer J;Bajramovic JJ
白细胞介素(IL)-1β是一种促炎细胞因子，在多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）的发病过程中发挥作用。然而，关于IL-1β在MS病变发展不同阶段的表达以及IL-1β在MS和EAE中的表达比较的详细研究尚缺乏。在这里，我们对MS患者脑组织中IL-1β的表达进行了广泛的表征，包括不同的MS病变类型，以及在EAE的恒河猴脑组织中。在恒河猴EAE脑组织中，我们观察到血管周围浸润和大脱髓鞘病变边缘的MHC类II+细胞中有明显的IL-1β染色。令人惊讶的是，染色定位于驻留的小胶质细胞或分化的巨噬细胞，而不是浸润的单核细胞，这表明IL-1β在中枢神经系统（CNS）内被诱导表达。相比之下，MS脑组织中的IL-1β染色则不那么明显。在活动性和慢性活动性MS病变的实质以及其他正常白质的MHC II级+小胶质细胞结节中发现染色。IL-1β仅在少数结节中表达，不能通过促炎和抗炎标志物的表达来区分。这些结节仅在多发性硬化症中发现，IL-1β+结节是否注定会进展为活动性病变，或者它们是否仅仅反映了对细胞应激的短暂反应，仍有待确定。尽管在EAE和MS中IL-1β表达的确切位置和相对强度不同，但这两种神经炎性疾病的染色模式最符合病变发展过程中IL-1β的表达在组织中而不是在周围被诱导的观点。本文的在线版本（doi:10.1186/s12974-016-0605-8）包含补充材料，可供授权用户使用。
Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a role in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Yet, detailed studies on IL-1β expression in different stages of MS lesion development and a comparison of IL-1β expression in MS and EAE are lacking. Here, we performed an extensive characterization of IL-1β expression in brain tissue of MS patients, which included different MS lesion types, and in brain tissue of rhesus macaques with EAE. In rhesus EAE brain tissue, we observed prominent IL-1β staining in MHC class II+ cells within perivascular infiltrates and at the edges of large demyelinating lesions. Surprisingly, staining was localized to resident microglia or differentiated macrophages rather than to infiltrating monocytes, suggesting that IL-1β expression is induced within the central nervous system (CNS). By contrast, IL-1β staining in MS brain tissue was much less pronounced. Staining was found in the parenchyma of active and chronic active MS lesions and in nodules of MHC class II+ microglia in otherwise normal appearing white matter. IL-1β expression was detected in a minority of the nodules only, which could not be distinguished by the expression of pro- and anti-inflammatory markers. These nodules were exclusively found in MS, and it remains to be determined whether IL-1β+ nodules are destined to progress into active lesions or whether they merely reflect a transient response to cellular stress. Although the exact localization and relative intensity of IL-1β expression in EAE and MS is different, the staining pattern in both neuroinflammatory disorders is most consistent with the idea that the expression of IL-1β during lesion development is induced in the tissue rather than in the periphery. The online version of this article (doi:10.1186/s12974-016-0605-8) contains supplementary material, which is available to authorized users.