低密度粒细胞在自身免疫性疾病中的病理生理作用

Pathophysiological effect of low-density granulocytes in autoimmune diseases

疾病期增强活化异常的中性粒细胞可能导致组织损伤和异常免疫应答。最近报道了一种中性粒细胞亚群,即从系统性红斑狼疮(systemic lupus erythematosus,SLE)患者的外周血单核细胞部分分离出的低密度粒细胞(low-density granulocytes,LDGs)。LDGs的表型和功能不同于循环中性粒细胞,其具有促炎性和致病性功能,包括内皮细胞毒性和合成干扰素-I的能力。此外,LDGs容易形成中性粒细胞胞外诱捕网(low-density granulocytes,NETs),NETs促进自身抗原外显与器官损伤。阐明LDGs的的致病作用,有可能为SLE和其他自身免疫性疾病设计新的治疗策略。

Tissue damage and potential aberrant immune responses could be caused by increased activation of abnormal neutrophils during the progression of autoimmune diseases. Recent studies have demonstrated a distinct subset of neutrophils isolated from the fraction of peripheral blood mononuclear cells（PBMCs） in the patients with systemic lupus erythematosus（SLE）, which has been defined as low-density granulocytes（LDGs）. Compared with the circulating neutrophils in healthy individuals, LDGs show distinct phenotype and abnormal functions. They demonstrate proinflammatory activity and pathogenic effects, including injury to endothelial cells and enhanced capability to synthesize type I interferons（IFN-I）. Moreover, LDGs facilitate the formation of neutrophil extracellular traps（NETs） which plays an important role in promoting autoantigen externalization and resulting in organ damage. With elucidation of the pathogenicity of LDGs, novel therapeutic modalities may be designed for the treatment of SLE and other autoimmune diseases in the near future.