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眼内树突状细胞是 HLA-B27 相关性急性前葡萄膜炎的特征。

Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis.

机构信息

Ophtha-Lab, Department of Ophthalmology, and Uveitis Centre at St. Franziskus Hospital, Münster, Germany.

Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, Muenster, Germany.

出版信息

Elife. 2021 Nov 16;10:e67396. doi: 10.7554/eLife.67396.

DOI:10.7554/eLife.67396
PMID:34783307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8594918/
Abstract

Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.

摘要

葡萄膜炎是一组异质性的炎症性眼病，其特征为白细胞浸润葡萄膜组织。与 HLA 单倍型 B27（HLA-B27）相关的葡萄膜炎是葡萄膜炎的常见亚型，也是典型的眼免疫介导疾病。由于可利用的生物材料有限，以及随后的技术限制，导致目前人们对驱动人类葡萄膜炎的局部免疫机制的认识还很有限。在这里，我们通过结合单细胞 RNA 测序、流式细胞术和蛋白质分析，首次对 HLA-B27 阳性（n=4）和阴性（n=2）前葡萄膜炎以及感染性眼内炎对照（n=1）的眼内白细胞进行了高分辨率特征描述。在这两种葡萄膜炎亚型中，眼细胞浸润主要由淋巴细胞组成，而在感染性眼内炎中则由髓样细胞组成。HLA-B27 阳性葡萄膜炎仅表现为浆细胞样和经典树突状细胞（cDC）浸润。此外，cDC 是预测局部细胞间通讯的核心。这表明 HLA-B27 阳性葡萄膜炎存在独特的眼白细胞浸润模式，与树突状细胞有关。

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