PDF(Pubmed)
Abstract：
UNASSIGNED: Non-infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet\'s disease (BD) and Vogt-Koyanagi-Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD can show similar clinical manifestations, but the underlying immunopathogenesis remains unclear.
UNASSIGNED: To understand immune landscapes in inflammatory eye tissues, we performed single-cell RNA paired with T cell receptor (TCR) sequencing of immune cell infiltrates in aqueous humour from six patients with BD (N = 3) and VKHD (N = 3) uveitis patients.
UNASSIGNED: Although T cells strongly infiltrated in both types of autoimmune uveitis, myeloid cells only significantly presented in BD uveitis but not in VKHD uveitis. Conversely, VKHD uveitis but not BD uveitis showed an overwhelming dominance by CD4+ T cells (> 80%) within the T cell population due to expansion of CD4+ T cell clusters with effector memory (Tem) phenotypes. Correspondingly, VKHD uveitis demonstrated a selective expansion of CD4+ T cell clones which were enriched in pro-inflammatory Granzyme H+ CD4+ Tem cluster and showed TCR and Th1 pathway activation. In contrast, BD uveitis showed a preferential expansion of CD8+ T cell clones in pro-inflammatory Granzyme H+ CD8+ Tem cluster, and pathway activation for cytoskeleton remodelling, cellular adhesion and cytotoxicity.
UNASSIGNED: Single-cell analyses of ocular tissues reveal distinct landscapes of immune cell infiltration and T-cell clonal expansions between VKHD and BD uveitis. Preferential involvements of pro-inflammatory CD4+ Th1 cells in VKHD and cytotoxic CD8+ T cells in BD suggest a difference in disease immunopathogenesis and can guide precision disease management.
UNASSIGNED: To understand immune landscapes in inflammatory eye tissues, we performed single-cell RNA paired with T cell receptor (TCR) sequencing of immune cell infiltrates in aqueous humour from six patients with BD (N = 3) and VKHD (N = 3) uveitis patients.
UNASSIGNED: Although T cells strongly infiltrated in both types of autoimmune uveitis, myeloid cells only significantly presented in BD uveitis but not in VKHD uveitis. Conversely, VKHD uveitis but not BD uveitis showed an overwhelming dominance by CD4+ T cells (> 80%) within the T cell population due to expansion of CD4+ T cell clusters with effector memory (Tem) phenotypes. Correspondingly, VKHD uveitis demonstrated a selective expansion of CD4+ T cell clones which were enriched in pro-inflammatory Granzyme H+ CD4+ Tem cluster and showed TCR and Th1 pathway activation. In contrast, BD uveitis showed a preferential expansion of CD8+ T cell clones in pro-inflammatory Granzyme H+ CD8+ Tem cluster, and pathway activation for cytoskeleton remodelling, cellular adhesion and cytotoxicity.
UNASSIGNED: Single-cell analyses of ocular tissues reveal distinct landscapes of immune cell infiltration and T-cell clonal expansions between VKHD and BD uveitis. Preferential involvements of pro-inflammatory CD4+ Th1 cells in VKHD and cytotoxic CD8+ T cells in BD suggest a difference in disease immunopathogenesis and can guide precision disease management.
摘要：
■非感染性葡萄膜炎通常继发于全身性自身免疫性疾病，以Behçet病（BD）和Vogt-Koyanagi-Harada病（VKHD）为两个最常见的原因。BD和VKHD的葡萄膜炎可以表现出相似的临床表现，但潜在的免疫发病机制仍不清楚。
■为了了解炎症眼组织的免疫景观，我们对6例BD(N=3)和VKHD(N=3)葡萄膜炎患者的房水免疫细胞浸润进行了单细胞RNA配对T细胞受体(TCR)测序.
■尽管T细胞在两种类型的自身免疫性葡萄膜炎中均有强烈浸润，骨髓细胞仅在BD葡萄膜炎中显著存在，而在VKHD葡萄膜炎中不显著存在。相反，由于具有效应记忆(Tem)表型的CD4+T细胞簇的扩增,VKHD葡萄膜炎而非BD葡萄膜炎显示T细胞群内CD4+T细胞(>80%)的压倒性优势。相应地,VKHD葡萄膜炎显示了CD4+T细胞克隆的选择性扩增,其富含促炎性颗粒酶H+CD4+Tem簇,并显示TCR和Th1途径激活。相比之下,BD葡萄膜炎在促炎性粒酶H+CD8+Tem簇中显示CD8+T细胞克隆的优先扩增，和细胞骨架重塑的途径激活，细胞粘附和细胞毒性。
眼组织的单细胞分析揭示了VKHD和BD葡萄膜炎之间免疫细胞浸润和T细胞克隆扩增的不同景观。VKHD中的促炎性CD4Th1细胞和BD中的细胞毒性CD8T细胞的优先参与表明疾病免疫发病机制的差异，并可以指导精确的疾病管理。
■为了了解炎症眼组织的免疫景观，我们对6例BD(N=3)和VKHD(N=3)葡萄膜炎患者的房水免疫细胞浸润进行了单细胞RNA配对T细胞受体(TCR)测序.
■尽管T细胞在两种类型的自身免疫性葡萄膜炎中均有强烈浸润，骨髓细胞仅在BD葡萄膜炎中显著存在，而在VKHD葡萄膜炎中不显著存在。相反，由于具有效应记忆(Tem)表型的CD4+T细胞簇的扩增,VKHD葡萄膜炎而非BD葡萄膜炎显示T细胞群内CD4+T细胞(>80%)的压倒性优势。相应地,VKHD葡萄膜炎显示了CD4+T细胞克隆的选择性扩增,其富含促炎性颗粒酶H+CD4+Tem簇,并显示TCR和Th1途径激活。相比之下,BD葡萄膜炎在促炎性粒酶H+CD8+Tem簇中显示CD8+T细胞克隆的优先扩增，和细胞骨架重塑的途径激活，细胞粘附和细胞毒性。
眼组织的单细胞分析揭示了VKHD和BD葡萄膜炎之间免疫细胞浸润和T细胞克隆扩增的不同景观。VKHD中的促炎性CD4Th1细胞和BD中的细胞毒性CD8T细胞的优先参与表明疾病免疫发病机制的差异，并可以指导精确的疾病管理。
