IL-23 prevents IL-13-dependent tissue repair associated with Ly6Clo monocytes in Entamoeba histolytica-induced liver damage
IL-23 prevents IL-13-dependent tissue repair associated with Ly6Clo monocytes in Entamoeba histolytica-induced liver damage
复制标题
DOI：
10.1016/j.jhep.2016.01.013
复制
发表时间：
2016-05-01
影响因子：
25.7
通讯作者：
Lotter, Hannelore
中科院分区：
文献类型：
--
作者：
Noll, Jill;Helk, Elena;Lotter, Hannelore
背景和目标：IL-23/IL-17轴在自身免疫性疾病的发病机制和感染的病理后果中起重要作用。我们以前表明，炎症单核细胞介导的免疫病理机制是原生动物寄生虫溶组织内阿米巴引起的严重局灶性肝损伤的基础。在此，我们分析了IL-23/IL-17轴对寄生虫诱导的肝损伤的诱导和随后的恢复的贡献。通过磁共振成像分析溶组织滋养体和疾病发作和恢复。通过qPCR、微阵列、FACS分析和免疫组织化学检测感染过程中肝脏特异性基因和蛋白的表达。结果：IL-23 p19（-/-）、IL-17 A/F（-/-）和CCR 2（-/-）感染小鼠的肝损伤较WT小鼠明显减轻。IL-23 p19（-/-）小鼠显示IL-17和CCL 2 mRNA和蛋白质的蓄积减少。在IL-23 p19（-/-）小鼠中，产生IL-13的CD 11b（+）Ly 6C（lo）单核细胞数量的增加与疾病减轻相关。IL-23 p19（-/-）小鼠中IL-13的免疫耗竭逆转了这种衰减，并且用IL-13/抗IL-13-mAb复合物治疗感染的WT小鼠支持肝脏恢复。结论：IL-23/IL-17轴在肝阿米巴病的免疫病理学中起关键作用。CD 11b（+）Ly 6C（lo）单核细胞分泌的IL-13可能与肝损伤的恢复有关。IL-13/抗IL-13-mAb复合物模拟了这种功能，表明了一种新的治疗选择，以支持肝损伤后的组织愈合。(C)2016年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage.Methods: IL-23p19(-/-), CCR2(-/-), and wild-type (WT) mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. Liver-specific gene and protein expression during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19(-/-) and WT mice to investigate the role of IL-13 in disease outcome.Results: Liver damage in infected IL-23p19(-/-), IL-17A/F-/-, and CCR2(-/-) mice was strongly attenuated compared with that in WT mice. IL-23p19(-/-) mice showed reduced accumulation of IL-17 and CCL2 mRNA and proteins. Increased numbers of IL-13 producing CD11b(+)Ly6C(lo) monocytes were associated with disease attenuation in IL-23p19(-/-) mice. Immuno-depletion of IL-13 in IL-23p19(-/-) mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery.Conclusions: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL-13 secreted by CD11b(+)Ly6C(lo) monocytes may be associated with recovery from liver damage. An IL-13/anti-IL13-mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.