Division of General Pathology.
Division of Hematology and Bone Marrow Transplant Unit.
Blood. 2017 Mar 9;129(10):1343-1356. doi: 10.1182/blood-2016-04-713206. Epub 2017 Jan 4.
The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66bCD10 neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66bCD10 neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.
鉴定离散中性粒细胞群体，并对其免疫调节特性进行特征描述，是一个备受广泛研究关注的新兴课题。在这方面，已经在几种急性和慢性炎症性疾病中描述了存在发挥免疫抑制或促炎作用的循环 CD66b 中性粒细胞群体。然而，由于缺乏特异性标志物，这些中性粒细胞群体的确切表型和成熟状态仍不清楚。在此，我们报告 CD10（也称为常见急性淋巴细胞白血病抗原、中性内肽酶或脑啡肽酶）可用作标志物，在炎症条件下存在的循环 CD66b 中性粒细胞异质性群体中，它可明确区分成熟和未成熟的中性粒细胞。因此，我们观察到，先前描述的在粒细胞集落刺激因子（G-CSF）处理供体（GD）的循环中出现的免疫抑制中性粒细胞群体由成熟的 CD66bCD10 中性粒细胞组成，这些中性粒细胞显示出激活的表型。这些中性粒细胞通过 CD18 介导的接触依赖性精氨酸酶 1 释放来抑制 T 细胞的增殖和干扰素 γ（IFNγ）产生。相比之下，我们发现 GD 中也存在未成熟的 CD66bCD10 中性粒细胞，它们具有未成熟的形态，促进 T 细胞存活，并增强 T 细胞的增殖和 IFNγ 产生。总之，我们的研究结果揭示了在 GD 中，循环的成熟和未成熟中性粒细胞通过其 CD10 表达的差异发挥相反的免疫调节特性。因此，CD10 可用作区分急性或慢性炎症性疾病患者中存在的成熟中性粒细胞和未成熟中性粒细胞群体的表型标志物，并有助于它们的分离，以更好地定义其特定的免疫调节特性。
