在自身免疫性眼部炎症性疾病中，由TNFα-p38丝裂原活化蛋白激酶调节的具有成熟表型的CD1c+ mDC1增加。
Increased CD1c+ mDC1 with mature phenotype regulated by TNFα-p38 MAPK in autoimmune ocular inflammatory disease.
作者信息
Chen Ping, Denniston Alastair, Hannes Susan, Tucker William, Wei Lai, Liu Baoying, Xiao Tiaojiang, Hirani Sima, Li Zhiyu, Jawad Shayma, Si Han, Lee Richard W J, Sen H Nida, Nussenblatt Robert B
机构信息
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ophthalmology Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHSFT, Edgbaston, Birmingham B15 2WB, UK; Centre for Translational Inflammation Research, University of Birmingham, UK.
出版信息
Clin Immunol. 2015 May;158(1):35-46. doi: 10.1016/j.clim.2015.03.002. Epub 2015 Mar 14.
In this study we investigated the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c(+) mDC1 in uveitis patients. The increased CD1c(+) mDC1 exhibited high HLADR expression and less antigen uptake. CD1c(+) mDC1 were divided into two subpopulations. CD1c(hi) mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1c(lo) mDC1 subpopulation. Importantly, the CD1c(hi) mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD4(+)CD62L(-) T helper cell proliferation. The mature phenotype and function of CD1c(+) mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c(+) mDC1.
在本研究中，我们调查了血液中关键的髓样树突状细胞亚群CD1c(+)髓样树突状细胞1（mDC1）在自身免疫性葡萄膜炎患者中的作用。我们观察到葡萄膜炎患者血液中CD1c(+) mDC1显著增加。增加的CD1c(+) mDC1表现出高HLA-DR表达和较少的抗原摄取。CD1c(+) mDC1分为两个亚群。与CD1c(lo) mDC1亚群相比，CD1c(hi) mDC1亚群显示出较少的抗原摄取和较高的HLA-DR表达。重要的是，葡萄膜炎患者中CD1c(hi) mDC1亚群增加。在体外，以较低水平的抗原摄取为特征的成熟单核细胞衍生树突状细胞（MoDCs）诱导更多的CD4(+)CD62L(-) T辅助细胞增殖。CD1c(+) mDC1的成熟表型和功能通过p38丝裂原活化蛋白激酶（MAPK）依赖性途径由肿瘤坏死因子α（TNFα）调节。这些数据表明全身免疫反应的改变参与了自身免疫性葡萄膜炎的发病机制，并提示通过操纵血液中的CD1c(+) mDC1来减轻葡萄膜炎的治疗可能性。
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