Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.
Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.
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DOI：
10.3390/ijms22073623
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发表时间：
2021-03-31
影响因子：
5.6
通讯作者：
Sonoda KH
中科院分区：
文献类型：
--
作者：
Yawata N;Shirane M;Woon K;Lim X;Tanaka H;Kawano YI;Yawata M;Chee SP;Siak J;Sonoda KH
巨细胞病毒（CMV）主要在免疫抑制条件下引起临床问题。CMV相关性前葡萄膜炎（CMV-AU）是一种值得注意的新疾病实体，表现为免疫活性个体的复发性眼部炎症。由于患者人口统计学表明遗传背景和免疫衰老作为可能的潜在病理机制的贡献，我们结合细胞表型分析了队列的免疫遗传学，以鉴定CMV-AU的分子特征。在免疫细胞类型中，自然杀伤（NK）细胞是针对CMV的主要应答者。因此，我们首先在122例CMV-AU患者中表征了编码CMV相关人类NK细胞应答（杀伤细胞免疫球蛋白样受体（KIR）和HLA I类）差异的多态性基因变体。然后根据其遗传特征对病例进行分层，并通过流式细胞术分析NK细胞的人CMV相关标志物（CD 57，KLRG 1，NKG 2C）。编码强受体-配体相互作用的KIR 3DL 1和HLA I类组合在CMV-AU中以显著更高的频率存在。在这些情况下，NK细胞分析显示共表达CD 57和KLRG 1以及KIR 3DL 1和CMV识别NKG 2C受体的亚群扩增。这些发现表明CMV-AU发病机制可能涉及CMV应答NK细胞共表达CD 57/KLRG 1/NKG 2C，这些细胞在编码强受体-配体相互作用的KIR 3DL 1/HLA-B同种异型的遗传背景上发育。
Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor–ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor–ligand interactions.
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作者：
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