International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia.
Front Immunol. 2021 Nov 2;12:770515. doi: 10.3389/fimmu.2021.770515. eCollection 2021.
Neutrophils are innate immune cells with important roles in antimicrobial defense. However, impaired or dysregulated neutrophil function can result in host tissue damage, loss of homeostasis, hyperinflammation or pathological immunosuppression. A central link between neutrophil activation and immune outcomes is emerging to be the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, which is activated by neutrophil detection of a microbial threat pattern recognition receptors and results in inflammatory cytokine production. This potent pro-inflammatory pathway is also the target of several immunosuppressive drugs used for the treatment of autoimmune disorders, during solid organ and hematopoietic cell transplantations, and as a part of anti-cancer therapy: but what effects these drugs have on neutrophil function, and their broader consequences for immune homeostasis and microbial defense are not yet known. Here, we bring together the emerging literature describing pathology- and drug- induced neutrophil impairment, with particular focus on their effects on calcineurin-NFAT signaling in the innate immune compartment.
中性粒细胞是先天免疫系统的细胞，在抗微生物防御中起着重要作用。然而，中性粒细胞功能受损或失调会导致宿主组织损伤、失去内稳态、过度炎症或病理性免疫抑制。中性粒细胞激活和免疫结果之间的一个中心联系正在出现，那就是钙调神经磷酸酶-激活 T 细胞的核因子（NFAT）信号通路，它被中性粒细胞检测到微生物威胁模式识别受体激活，导致炎症细胞因子的产生。这种强大的促炎途径也是几种用于治疗自身免疫性疾病、实体器官和造血细胞移植以及癌症治疗的免疫抑制剂的靶点：但是这些药物对中性粒细胞功能有什么影响，以及它们对免疫稳态和微生物防御的更广泛影响尚不清楚。在这里，我们汇集了描述病理学和药物诱导的中性粒细胞损伤的新出现的文献，特别关注它们对先天免疫区钙调神经磷酸酶-NFAT 信号的影响。
