Heineke Marieke H, van Egmond Marjolein
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.
Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands.
Eur J Clin Invest. 2017 Feb;47(2):184-192. doi: 10.1111/eci.12716. Epub 2017 Jan 19.
Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor Fc?RI (CD89), leading to pro- or anti-inflammatory responses.
The aim of this review is to give a concise overview of the interplay between IgA, Fc?RI and neutrophils and to explore potential therapies for autoimmune diseases and cancer.
Crosslinking of FcαRI by IgA-immune complexes yields potent neutrophil activation and pro-inflammatory effector functions, including the recruitment of neutrophils. This can lead to neutrophil accumulation and tissue destruction during IgA-autoantibody mediated diseases. Conversely, for cancer treatment, the myriad of powerful neutrophil effector functions after targeting FcαRI may contribute to effective immunotherapy.
By interfering with or actively promoting the interaction between IgA and FcαRI, therapies for multiple maladies could be developed.
中性粒细胞通过执行多种杀伤机制参与第一道防线，包括吞噬作用、脱颗粒和释放中性粒细胞胞外陷阱。此外，它们可通过分泌细胞因子和趋化因子来协调适应性免疫系统。抗体调理作用通过与中性粒细胞表面的Fc受体结合，有助于病原体的识别。免疫球蛋白A（IgA）是黏膜部位最丰富的抗体，在体内平衡和免疫中具有多种功能。中性粒细胞和IgA可通过IgA Fc受体FcαRI（CD89）相互作用，从而引发促炎或抗炎反应。
本综述的目的是简要概述IgA、FcαRI和中性粒细胞之间的相互作用，并探索自身免疫性疾病和癌症的潜在治疗方法。
IgA免疫复合物使FcαRI交联可产生有效的中性粒细胞活化和促炎效应功能，包括中性粒细胞的募集。这可导致IgA自身抗体介导的疾病中中性粒细胞积聚和组织破坏。相反，对于癌症治疗，靶向FcαRI后大量强大的中性粒细胞效应功能可能有助于有效的免疫治疗。
通过干扰或积极促进IgA与FcαRI之间的相互作用，可开发针对多种疾病的治疗方法。
