CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of FcεRI

CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of FcεRI
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DOI:
10.1111/j.1365-2222.2006.02578.x
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发表时间:
2006-11-01
影响因子:
6.1
通讯作者:
Prussin, C.
Prussin, C.
中科院分区:
医学2区
文献类型:
--
作者:
Cheng, Y. X.;Foster, B.;Prussin, C.

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背景单核细胞表达的Fc β RI可通过多种机制影响单核细胞功能,从而潜在地影响过敏性炎症的产生。以前的研究在体内调节单核细胞Fc ε RI表达的环境IgE产生了相互矛盾的结果。目的我们假设,单核细胞Fc ε RI的表达是有限的一个特定的单核细胞亚群,并在该子集内Fc ε RI表面表达与血清IgE。从非过敏受试者(n = 14)和过敏性哮喘(n = 18)、嗜酸性粒细胞增多综合征(n = 2)、高IgE综合征(n = 6)和蠕虫感染(n = 4)受试者中采集血液。研究2:在奥马珠单抗临床试验中,在研究药物治疗前和治疗期间从过敏受试者中采集血液。结果在CD2(高)和CD2(低)单核细胞亚群中,Fc ε RI的表达显著高于CD2(低)单核细胞亚群(分别为31%和1.9%)。在哮喘和非特应性健康对照受试者中,CD2(低)单核细胞表达很少或检测不到Fc ε RI。在研究1中,在CD2(高)单核细胞亚群中,Fc ε RI表达与血清IgE高度相关,但在CD2(低)单核细胞亚群中不相关(R值分别为0.67和0.41)。在研究2中,奥马珠单抗(而不是安慰剂)导致CD 2(高)单核细胞亚群中的Fe epsilon RI表达显着且持续下降。结论CD 2定义了具有高Fe epsilon RI表达的单核细胞亚群,其幅度与血清IgE高度相关。因此,这种将CD2(高)单核细胞描述为携带Fc β RI的细胞的新描述表明,它们可能是抗IgE免疫调节治疗的潜在靶点。
Background Fc epsilon RI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte Fc epsilon RI expression by ambient IgE have yielded conflicting results.Objective We hypothesized that monocyte Fc epsilon RI expression is limited to a specific monocyte subset, and that within that subset Fc epsilon RI surface expression is correlated to serum IgE.Methods Study 1: Blood was obtained from non-allergic subjects (n = 14) and subjects with allergic asthma (n = 18), hypereosinophilic syndrome (n = 2), hyper-IgE syndrome (n = 6), and helminth infection (n = 4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface Fc epsilon RI expression was measured using flow cytometry.Results Fc epsilon RI expression was significantly greater in the CD2(high) vs. CD2(low) monocyte subsets (31% vs. 1.9% median Fc epsilon RI 1, respectively). In asthmatic and non-atopic healthy control subjects, CD2(low) monocytes expressed little or undetectable Fc epsilon RI. In study 1, Fc epsilon RI expression was highly correlated to serum IgE in the CD2(high), but not in the CD2(low) monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab, but not placebo, caused a significant and sustained decline in Fc epsilon RI expression within the CD2(high) monocyte subset.Conclusions CD2 defines a monocyte subset with high Fc epsilon RI expression, whose magnitude is highly correlated to serum IgE. As such, this new description of CD2(high) monocytes as Fc epsilon RI-bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies.