Abstract:
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 via 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.
摘要:
中性粒细胞是先天性免疫细胞,在抗菌防御中具有重要作用。然而,中性粒细胞功能受损或失调可导致宿主组织损伤,失去稳态,炎症过度或病理性免疫抑制。中性粒细胞活化和免疫结果之间的中心环节正在出现钙调磷酸酶-活化T细胞核因子(NFAT)信号通路,通过模式识别受体对微生物威胁的中性粒细胞检测而激活,并导致炎性细胞因子的产生。这种有效的促炎途径也是用于治疗自身免疫性疾病的几种免疫抑制药物的靶标。在实体器官和造血细胞移植期间,作为抗癌治疗的一部分:但是这些药物对中性粒细胞功能有什么影响,它们对免疫稳态和微生物防御的广泛影响尚不清楚。这里,我们汇集了描述病理和药物诱导的中性粒细胞损伤的新兴文献,特别关注它们对先天免疫区室中钙调磷酸酶-NFAT信号传导的影响。