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Cell Death Dis:经典树突状细胞在自身免疫性肝炎中的作用

2020-02-10 QQY MedSci原创

自身免疫性肝炎(AIH)是一种与先天性及适应性免疫系统相互作用的细胞群相关的坏死性炎性疾病。但经典树突状细胞(cDCs)对AIH的贡献及其潜在的机制仍知之甚少。 在AIH患者外周血中,成熟cDC的数量增加,与疾病的严重程度呈正相关。在实验性自身免疫性肝炎(EAH)中,可观察到成熟cDC在肝内积累,在外周血中也有所增加。因此,EAH小鼠骨髓来源的树突状细胞(BMDC)表现出比对照小鼠更强的促炎功能。

自身免疫性肝炎(AIH)是一种与先天性及适应性免疫系统相互作用的细胞群相关的坏死性炎性疾病。但经典树突状细胞(cDCs)对AIH的贡献及其潜在的机制仍知之甚少。

在AIH患者外周血中,成熟cDC的数量增加,与疾病的严重程度呈正相关。在实验性自身免疫性肝炎(EAH)中,可观察到成熟cDC在肝内积累,在外周血中也有所增加。因此,EAH小鼠骨髓来源的树突状细胞(BMDC)表现出比对照小鼠更强的促炎功能。

体外实验发现,ConA治疗可促进BMDC成熟,BMDC的特征是高表达MHC-II、共刺激分子及细胞因子分泌。 ConA还可诱导DCs中自噬相关蛋白的表达及自噬体的形成。

为了进一步研究ConA诱导的DC激活是否与自噬相关,研究人员采用3-MA及巴氟霉素A1阻断自噬,同时评估ConA诱导的DC的成熟及功能。当ConA诱导的BMDC与CD4+T细胞共培养时,3-MA和巴氟霉素A1可抑制其成熟状态及促炎细胞因子的分泌,并可减弱CD4+T细胞的增殖及分化。

本研究表明,cDCs可通过过度成熟来参与AIH的发病。异常自噬在AIH cDC的免疫成熟过程中起着至关重要的作用,致耐受性cDCs或可作为治疗AIH的一种新方法。

原始出处:

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    2020-08-29 维他命
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    2020-02-12 cy0328
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