Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
Allergy. 2022 Apr;77(4):1274-1284. doi: 10.1111/all.15073. Epub 2021 Sep 20.
Systemic sclerosis (SSc) is a multiorgan autoimmune disease characterized by inflammation, vascular modification, and progressive fibrosis of the skin and several visceral organs. Innate and adaptive immune cells, including myeloid, B and T cells, are believed to be central to the pathogenesis of SSc. However, the role and functional state of neutrophil granulocytes (neutrophils) are ill-defined in SSc.
We performed a prospective study of neutrophils freshly isolated from SSc patients and healthy donors (HD) by measuring in these neutrophils (i) functional cell surface markers, including CD16, CD62L, CD66b, CD66c, CXCR1, CXCR2, and CXCR4; (ii) cytokine-activated intracellular signal transducer and activator of transcription (STAT) pathways, such as phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6; (iii) production of neutrophil extracellular traps (NET) and intracellular myeloperoxidase (MPO); and (iv) phagocytosis of bacteria by the neutrophils.
Neutrophils of SSc patients expressed lower CD16 and CD62L and higher pSTAT3 and pSTAT6 compared to HD. Moreover, neutrophils of SSc patients lacked CXCR1 and CXCR2, the receptors responding to the potent neutrophil chemoattractant CXCL8. Neutrophils of SSc patients were also deficient in MPO levels, NET formation, and phagocytosis of bacteria.
Neutrophils of patients with SSc display several functional defects affecting cell migration, NET formation, and phagocytosis of bacteria.
系统性硬化症（SSc）是一种多器官自身免疫性疾病，其特征为炎症、血管改变和皮肤及若干内脏器官的进行性纤维化。先天和适应性免疫细胞，包括髓样细胞、B 细胞和 T 细胞，被认为是 SSc 发病机制的核心。然而，中性粒细胞（中性粒细胞）在 SSc 中的作用和功能状态仍未明确。
我们通过测量 SSc 患者和健康供体（HD）新鲜分离的中性粒细胞中的以下内容，对中性粒细胞进行了前瞻性研究：（i）功能细胞表面标志物，包括 CD16、CD62L、CD66b、CD66c、CXCR1、CXCR2 和 CXCR4；（ii）细胞因子激活的转录信号转导子和激活子（STAT）途径，如磷酸化 STAT3（pSTAT3）、pSTAT5 和 pSTAT6；（iii）中性粒细胞胞外诱捕网（NET）和细胞内髓过氧化物酶（MPO）的产生；以及（iv）中性粒细胞的细菌吞噬作用。
与 HD 相比，SSc 患者的中性粒细胞表达较低的 CD16 和 CD62L，较高的 pSTAT3 和 pSTAT6。此外，SSc 患者的中性粒细胞缺乏响应强中性粒细胞趋化因子 CXCL8 的受体 CXCR1 和 CXCR2。SSc 患者的中性粒细胞 MPO 水平、NET 形成和细菌吞噬作用也存在缺陷。
SSc 患者的中性粒细胞表现出多种影响细胞迁移、NET 形成和细菌吞噬作用的功能缺陷。
