Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.
Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.
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DOI：
10.1016/j.immuni.2021.04.001
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发表时间：
2021-06-08
期刊：
影响因子：
32.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Zhu B;Wu Y;Huang S;Zhang R;Son YM;Li C;Cheon IS;Gao X;Wang M;Chen Y;Zhou X;Nguyen Q;Phan AT;Behl S;Taketo MM;Mack M;Shapiro VS;Zeng H;Ebihara H;Mullon JJ;Edell ES;Reisenauer JS;Demirel N;Kern RM;Chakraborty R;Cui W;Kaplan MH;Zhou X;Goldrath AW;Sun J
组织巨噬细胞在动态平衡中自我更新，并在微生物感染时产生炎症介质。我们通过定义肺泡巨噬细胞(AM)中自我更新的中央调节因子WNT/β-连环蛋白通路的影响，研究了组织巨噬细胞的增殖和炎症特性之间的关系。WnT配体激活β-catenin抑制AM的增殖和干化，但促进炎症活动。在小鼠流感病毒性肺炎模型中，β-连环蛋白介导的AM炎症活动促进了急性宿主发病率；相反，AM增殖使修复的AM能够在病毒清除后重新聚集和组织恢复。机制上，WNT治疗促进β-连环蛋白-低氧诱导因子-1α相互作用和糖酵解依赖性炎症，同时抑制线粒体代谢，从而抑制AM的增殖。不同的HIF-1α活性可区分体内增生性和炎症性AM。这个β-连环蛋白-低氧诱导因子-1α轴在人AM中是保守的，而在新冠肺炎患者中，低氧诱导因子-1α表达增强与巨噬细胞炎症相关。因此，肺巨噬细胞的炎症和修复活动受β-连环蛋白-缺氧诱导因子-1α信号的调节，这对严重呼吸系统疾病的治疗具有重要意义。朱等人。通过定义肺泡巨噬细胞(AM)中自我更新调节因子WNT-β-连环蛋白通路的影响，研究组织巨噬细胞增殖和炎症特性之间的关系。他们的发现揭示了一个β-连环蛋白-低氧诱导因子-1α信号轴，该信号轴以促进增殖为代价促进炎性AM。这个轴在人类AM中是保守的，对严重呼吸系统疾病的治疗具有重要意义。
Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/β-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of β-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, β-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted β-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This β-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by β-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases. Zhu et al. examine the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt-β-catenin pathway, a regulator of self-renewal, in alveolar macrophages (AMs). Their findings reveal a β-catenin-HIF-1α signaling axis that promotes inflammatory AMs at the expense of proliferation. This axis is conserved in human AMs, with implications for the treatment of severe respiratory diseases.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.1
作者：
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通讯作者：
RABINOWITZ, S
影响因子：
5.8
作者：
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通讯作者：
Won, Misun
影响因子：
9
作者：
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通讯作者：
Perlman S
影响因子：
30.5
作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
通讯作者：
Wack, Andreas