Genomic Medicine Department, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Avda de la Ilustración 114, 18016, Granada, Spain.
Clin Rev Allergy Immunol. 2017 Oct;53(2):198-218. doi: 10.1007/s12016-017-8606-7.
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors. In this review, we summarize the current knowledge about the role of the main myeloid populations in the induction and maintenance of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary antiphospholipid antibody syndrome (PAPS), systemic sclerosis (SSc), and Sjögren's syndrome (SjS), based on the data from both mouse preclinical models and patients. According to these data, our challenge in the next few years is to better dissect the fine mechanisms underlying the pathological role of myeloid cells in these diseases in order to define specific cell subsets or proteins that can be potential targets for drug development.
系统性自身免疫性疾病(SADs)涵盖了广泛的临床症状,反映了其复杂的病理生理学。多种与固有免疫系统相关的机制是这些疾病自身耐受丧失的起源,对于大多数疾病而言,髓系白细胞是关键的作用者。单核细胞、巨噬细胞、树突状细胞和中性粒细胞是位于固有免疫和适应性免疫界面的一线免疫效应细胞。它们在组织损伤相关分子模式(DAMPs)的局部和全身反应中起着至关重要的作用,通过表达趋化因子、共刺激或耐受原性因子来决定局部免疫反应的强度、方向和持续时间。在这篇综述中,我们根据来自小鼠临床前模型和患者的数据,总结了主要髓系细胞群在诱导和维持系统性红斑狼疮(SLE)、类风湿关节炎(RA)、原发性抗磷脂抗体综合征(PAPS)、系统性硬皮病(SSc)和干燥综合征(SjS)中的作用的最新知识。根据这些数据,我们未来几年的挑战是更好地剖析髓系细胞在这些疾病中的病理作用的精细机制,以确定可以作为药物开发潜在靶点的特定细胞亚群或蛋白。