The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines.
The MHC class II antigen presentation pathway in human monocytes differs by subset and is regulated by cytokines.
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人类单核细胞中的MHC II类抗原表现途径通过子集有所不同，受细胞因子调节。
DOI：
10.1371/journal.pone.0183594
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mellins ED
中科院分区：
文献类型：
--
作者：
Lee J;Tam H;Adler L;Ilstad-Minnihan A;Macaubas C;Mellins ED
单核细胞在先天性和适应性免疫系统中发挥着关键作用，执行吞噬作用、呈递抗原并产生细胞因子。它们是一个异质群体，在人类中被分为经典、中间和非经典子集，但这些子集的作用尚不完全清楚。在本研究中，我们研究了 MHC II 类 (MHCII) 和相关分子的表达模式，发现中间单核细胞表达最高水平的 MHC 分子、HLA-DR（在 n = 30 个样本中测试）、HLA-DP (n = 30) 和 HLA-DQ (n = 10)。 HLA-DM (n = 30) 催化 MHC 分子上的肽交换，在中间单核细胞中也以最高水平表达。为了测量 HLA-DM 功能，我们测量了 MHCII 结合的 CLIP（II 类不变链肽，n = 23）的水平，该肽被 HLA-DM 交换为其他肽。我们计算了 CLIP:MHCII 比率，将 CLIP 水平标准化为 MHCII 水平，发现中间单核细胞的 CLIP:MHCII 比率最低。我们分离了不同的单核细胞亚群（总共 7 个样本），并分析了它们对选定细胞因子的反应作为单核细胞激活模型：两种 M1 极化细胞因子（IFNγ、GM-CSF）、一种 M2 极化细胞因子（IL-4）和 IL-10。经典单核细胞响应刺激性细胞因子（IFNγ、GM-CSF、IL-4）而表现出 II 类途径表达的最大增加。暴露 IL-10 后，所有三个子集都会降低 HLA-DR 水平。我们的研究结果表明，中间单核细胞是最有效的组成型抗原呈递亚群，经典单核细胞在炎症反应过程中被招募发挥抗原呈递作用，并且IL-10在所有亚群中负向调节这一功能。
Monocytes play a critical role in the innate and adaptive immune systems, performing phagocytosis, presenting antigen, and producing cytokines. They are a heterogeneous population that has been divided in humans into classical, intermediate, and non-classical subsets, but the roles of these subsets are incompletely understood. In this study, we investigated the expression patterns of MHC class II (MHCII) and associated molecules and find that the intermediate monocytes express the highest levels of the MHC molecules, HLA-DR (tested in n = 30 samples), HLA-DP (n = 30), and HLA-DQ (n = 10). HLA-DM (n = 30), which catalyzes the peptide exchange on the MHC molecules, is also expressed at the highest levels in intermediate monocytes. To measure HLA-DM function, we measured levels of MHCII-bound CLIP (class II invariant chain peptide, n = 23), which is exchanged for other peptides by HLA-DM. We calculated CLIP:MHCII ratios to normalize CLIP levels to MHCII levels, and found that intermediate monocytes have the lowest CLIP:MHCII ratio. We isolated the different monocyte subsets (in a total of 7 samples) and analyzed their responses to selected cytokines as model of monocyte activation: two M1-polarizing cytokines (IFNγ, GM-CSF), an M2-polarizing cytokine (IL-4) and IL-10. Classical monocytes exhibit the largest increases in class II pathway expression in response to stimulatory cytokines (IFNγ, GM-CSF, IL-4). All three subsets decrease HLA-DR levels after IL-10 exposure. Our findings argue that intermediate monocytes are the most efficient constitutive antigen presenting subset, that classical monocytes are recruited into an antigen presentation role during inflammatory responses and that IL-10 negatively regulates this function across all subsets.
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