Laboratory of Immunobiology, Rega Institute, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Laboratory of Pediatric Immunology, University Hospital Gasthuisberg, Herestraat 49, Box 7003, B-3000 Leuven, Belgium.
Cytokine Growth Factor Rev. 2015 Jun;26(3):263-80. doi: 10.1016/j.cytogfr.2014.10.001. Epub 2014 Oct 28.
Hemophagocytic lymphohistiocytosis (HLH) comprises a group of life-threatening immune disorders classified into primary or secondary HLH. The former is caused by mutations in genes involved in granule-mediated cytotoxicity, the latter occurs in a context of infections, malignancies or autoimmune/autoinflammatory disorders. Both are characterized by systemic inflammation, severe cytokine storms and immune-mediated organ damage. Despite recent advances, the pathogenesis of HLH remains incompletely understood. Animal models resembling different subtypes of HLH are therefore of great value to study this disease and to uncover novel treatment strategies. In this review, all known animal models of HLH will be discussed, highlighting findings on cell types, cytokines and signaling pathways involved in disease pathogenesis and extrapolating therapeutic implications for the human situation.
噬血细胞性淋巴组织细胞增生症(HLH)是一组危及生命的免疫性疾病,分为原发性或继发性 HLH。前者由颗粒介导的细胞毒性相关基因的突变引起,后者发生在感染、恶性肿瘤或自身免疫/炎症性疾病的背景下。两者均表现为全身炎症、严重细胞因子风暴和免疫介导的器官损伤。尽管最近取得了进展,但 HLH 的发病机制仍不完全清楚。因此,类似于不同 HLH 亚型的动物模型对于研究这种疾病和发现新的治疗策略具有重要价值。在这篇综述中,将讨论所有已知的 HLH 动物模型,重点介绍参与疾病发病机制的细胞类型、细胞因子和信号通路的研究结果,并推断出对人类情况的治疗意义。