IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum-infected mice.
IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum-infected mice.
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IL-7抑制巨噬细胞自噬并促进日本血吸虫感染小鼠的肝脏病理学
DOI：
10.1111/jcmm.13610
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发表时间：
2018-07
影响因子：
5.3
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Zhu J;Zhang W;Zhang L;Xu L;Chen X;Zhou S;Xu Z;Xiao M;Bai H;Liu F;Su C
在日本血吸虫病和曼氏血吸虫病中，寄生虫卵被困在宿主肝脏中会引起严重的肝脏肉芽肿性炎症，随后导致门静脉周围纤维化、门静脉高压、出血甚至死亡。巨噬细胞在血吸虫病期间肉芽肿形成和肝纤维化的发展中至关重要。然而，巨噬细胞自噬的异常调节是否对血吸虫病肝脏免疫病理学的发展有影响仍有待阐明。本研究表明，日本血吸虫（Schistosoma japonicum，S.日本血吸虫卵抗原（SEA）触发的巨噬细胞自噬限制了宿主肝脏病理学的发展。然而，S.日本血吸虫感染诱导的IL-7显著抑制SEA触发的巨噬细胞自噬，这导致肝脏病理学增强。此外，抗IL-7中和抗体或抗CD 127阻断抗体治疗增加巨噬细胞自噬并抑制肝脏病理学。最后，我们证明了IL-7通过激活AMP活化蛋白激酶（AMPK）保护巨噬细胞免受SEA诱导的自噬。我们的研究揭示了IL-7在巨噬细胞自噬中的新作用，并将AMPK确定为IL-7-IL-7 R信号传导的新型下游介质，并表明通过靶向IL-7-IL-7 R信号传导来操纵巨噬细胞自噬可能有可能改善血吸虫病肝脏发病机制的治疗选择。
In schistosomiasis japonica and mansoni, parasite eggs trapped in host liver elicit severe liver granulomatous inflammation that subsequently leads to periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages are critical for granuloma formation and the development of liver fibrosis during schistosomiasis. However, whether the aberrant regulation of macrophage autophagy has an effect on the development of liver immunopathology in schistosomiasis remains to be elucidated. In this study, we showed that Schistosoma japonicum (S. japonicum) egg antigen (SEA)‐triggered macrophage autophagy limited the development of pathology in host liver. However, engagement of IL‐7 receptor (IL‐7R/CD127) on macrophages by S. japonicum infection‐induced IL‐7 significantly suppressed SEA‐triggered macrophage autophagy, which led to an enhanced liver pathology. In addition, anti‐IL‐7 neutralizing antibody or anti‐CD127 blocking antibody treatment increased macrophage autophagy and suppressed liver pathology. Finally, we demonstrated that IL‐7 protects macrophage against SEA‐induced autophagy through activation of AMP‐activated protein kinase (AMPK). Our study reveals a novel role for IL‐7 in macrophage autophagy and identifies AMPK as a novel downstream mediator of IL‐7‐IL‐7R signalling and suggests that manipulation of macrophage autophagy by targeting IL‐7‐IL‐7R signalling may have the potential to lead to improved treatment options for liver pathogenesis in schistosomiasis.
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影响因子：
3.1
作者：
Wolowczuk, I;Nutten, S;Auriault, C
通讯作者：
Auriault, C
影响因子：
9
作者：
通讯作者：
--
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.
影响因子：
5.4
作者：
Hernandez, HJ;Wang, Y;Stadecker, MJ
通讯作者：
Stadecker, MJ
影响因子：
2.2
作者：
Roye, O;Delacre, M;Wolowczuk, I
通讯作者：
Wolowczuk, I