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Low-density neutrophils in chronic graft versus host disease (cGVHD) are primarily immature CD10– and enhance T cell activation
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2021-05-01 , DOI: 10.1111/cei.13612
Nick C Matthews 1 , Charlotte S Burton 1 , Arun Alfred 1
Affiliation  

Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogeneic haematopoietic stem cell transplantation. Low density neutrophils (LDNs) in autoimmunity, which shares disease features with cGVHD, are proinflammatory, whereas those in cancer and sepsis suppress T cell immunity. Mature LDNs can be distinguished from immature LDNs on the basis of expression of CD10 and suppressive neutrophils can be identified using lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. The functionality of LDNs in cGVHD has not been specifically investigated. Here, we have determined the relative contribution of immature and mature neutrophils to LDNs in cGVHD and assessed whether these were suppressive or potentially proinflammatory. Peripheral blood LDNs and normal density neutrophils (NDNs) from 30 cGVHD patients and NDNs from 10 healthy controls (HCs) were immunophenotyped by flow cytometry. The ability of LDNs and NDNs to influence T cell proliferation and cytokine production in co-cultures was quantified. To further characterize LDNs, their propensity to undergo constitutive apoptosis and differentiate ex vivo was assessed.

中文翻译:

慢性移植物抗宿主病 (cGVHD) 中的低密度中性粒细胞主要是未成熟的 CD10-并增强 T 细胞活化

慢性移植物宿主病(cGVHD)是异基因造血干细胞移植的常见并发症。自身免疫中的低密度中性粒细胞 (LDN) 与 cGVHD 具有共同的疾病特征,具有促炎作用,而癌症和败血症中的低密度中性粒细胞 (LDN) 可抑制 T 细胞免疫。根据 CD10 的表达,可以将成熟的 LDN 与未成熟的 LDN 区分开来,并且可以使用凝集素样氧化低密度脂蛋白受体 1 (LOX-1) 的表达来识别抑制性中性粒细胞。尚未专门研究 cGVHD 中 LDN 的功能。在这里,我们确定了未成熟和成熟中性粒细胞对 cGVHD 中 LDN 的相对贡献,并评估了这些是抑制性还是潜在的促炎性。通过流式细胞术对来自 30 名 cGVHD 患者的外周血 LDN 和正常密度中性粒细胞 (NDN) 和来自 10 名健康对照 (HC) 的 NDN 进行免疫表型分析。量化了 LDN 和 NDN 在共培养中影响 T 细胞增殖和细胞因子产生的能力。为了进一步表征 LDN,它们倾向于经历组成性细胞凋亡和分化离体进行了评估。
更新日期:2021-05-01
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