MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFNγ-independent fashion and during development.
MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFNγ-independent fashion and during development.
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DOI：
10.1038/srep24251
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发表时间：
2016-04-15
影响因子：
4.6
通讯作者：
Ferretti P
中科院分区：
文献类型：
--
作者：
Vagaska B;New SE;Alvarez-Gonzalez C;D'Acquisto F;Gomez SG;Bulstrode NW;Madrigal A;Ferretti P
非炎症状态下主要组织相容性抗原2类（MHC-II）的表达通常与神经系统无关。人胚胎/胎儿脑源性神经干细胞（hNSC）和来自脐带（UC-MSC）和儿科脂肪组织（ADSC）的具有神经发生潜能的人间充质干细胞的免疫原性的比较分析，同时突出了它们的免疫原性的差异，使我们发现在人CNS发育期间体内共表达神经标记物SOX 2和MHC-II抗原的神经细胞亚群。hNSC中的MHC-II蛋白是功能性的，并且在沿着不同谱系分化时受到不同的调节。使用炎性细胞因子IFNγ模拟炎性反应诱导星形胶质细胞和hNSCs中的MHC-II上调，但在未分化或分化的UC-MSC和ADSC中均未诱导MHC-II上调，尽管IFNγ受体表达相当。总之，UC-MSC和ADSC两者的低免疫原性支持它们对于同种异体疗法的适用性，而hNSC及其后代的显著免疫原性可能至少部分地成为在胚胎神经细胞移植后的一些患者中报道的负面作用的基础。至关重要的是，我们第一次表明，MHC-II在发育中的人脑中的表达并不局限于小胶质细胞，如前所述，但存在于离散的神经祖细胞亚群中，并且似乎独立于炎症刺激进行调节。
Expression of major histocompatibility antigens class-2 (MHC-II) under non-inflammatory conditions is not usually associated with the nervous system. Comparative analysis of immunogenicity of human embryonic/fetal brain-derived neural stem cells (hNSCs) and human mesenchymal stem cells with neurogenic potential from umbilical cord (UC-MSCs) and paediatric adipose tissue (ADSCs), while highlighting differences in their immunogenicity, led us to discover subsets of neural cells co-expressing the neural marker SOX2 and MHC-II antigen in vivo during human CNS development. MHC-II proteins in hNSCs are functional, and differently regulated upon differentiation along different lineages. Mimicking an inflammatory response using the inflammatory cytokine IFNγ induced MHC-II up-regulation in both astrocytes and hNSCs, but not in UC-MSCs and ADSCs, either undifferentiated or differentiated, though IFNγ receptor expression was comparable. Together, hypoimmunogenicity of both UC-MSCs and ADSCs supports their suitability for allogeneic therapy, while significant immunogenicity of hNSCs and their progeny may at least in part underlie negative effects reported in some patients following embryonic neural cell grafts. Crucially, we show for the first time that MHC-II expression in developing human brains is not restricted to microglia as previously suggested, but is present in discrete subsets of neural progenitors and appears to be regulated independently of inflammatory stimuli.