Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury
Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury
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巨噬细胞表型转换协调急性胰腺炎损伤后的炎症和修复/再生
DOI：
10.1016/j.ebiom.2020.102920
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发表时间：
2020-08-01
期刊：
影响因子：
11.1
通讯作者：
Xue, Jing
中科院分区：
文献类型：
--
作者：
Wu, Jinghua;Zhang, Li;Xue, Jing
背景资料：损伤后胰腺再生受损或过度活跃，可导致外分泌功能不全或复发/慢性胰腺炎，并可能致癌。巨噬细胞是再生胰腺中最丰富的免疫细胞，但它们的表型和作用仍然不明确defined.Method：使用雨蛙素诱导的急性胰腺炎（AP）模型，我们研究了动态景观胰腺巨噬细胞在整个急性炎症再生阶段的流式细胞术和RNA-seq分析。巨噬细胞脂质体耗竭，IL-4 ra（-/-）小鼠以及抑制剂被用来阐明胰腺regeneration.Findings过程中的作用和调节机制的巨噬细胞：我们发现，M1巨噬细胞占主导地位的AP的促炎阶段，而M2样巨噬细胞占主导地位的胰腺修复/再生。在再生早期或晚期消耗巨噬细胞分别显著阻断腺泡导管化生（ADM）或延迟炎症消退。此外，巨噬细胞的交替激活部分依赖于IL-4 RA信号，胰腺巨噬细胞中的ECM/AKT激活促进组织regeneration.Interpretation过程中的炎症消退：我们的研究结果说明了AP修复/再生过程中巨噬细胞的动态表型和功能，帮助我们更好地了解胰腺再生的机制，并为新的治疗策略提供线索。(c)2020作者（S）由爱思唯尔公司出版
Background: Impaired or hyperactive pancreas regeneration after injury would cause exocrine insufficiency or recurrent / chronic pancreatitis and potentially carcinogenesis. Macrophages are the most abundant immune cells in the regenerative pancreas, however their phenotype and role remain poorly defined.Method: Using caerulein-induced acute pancreatitis (AP) model, we examined the dynamic landscape of pancreatic macrophages throughout the acute inflammation to regeneration phases by flow cytometric and RNA-seq analyses. Liposome depletion of macrophages, Il4ra(-/-) mice as well as inhibitors were used to elucidate the role and regulatory mechanism of macrophages during pancreatic regeneration.Findings: We found that M1 macrophages dominated in the pro-inflammatory phase of AP, while M2-like macrophages dominated during pancreas repair/regeneration. Depletion of macrophages at early or late regenerative stage dramatically blocked the acinar-ductal metaplasia (ADM) or delayed inflammation resolution, respectively. Moreover, alternative activation of macrophages was partially dependent on IL-4RA signaling, and ECM/AKT activation in pancreatic macrophages facilitated inflammation resolution during tissue regeneration.Interpretation: Our findings illustrate a dynamic phenotype and function of macrophages during AP repair/regeneration, helping us better understand the mechanism of pancreatic regeneration and providing clues for novel therapeutic strategy. (c) 2020 The Author(s). Published by Elsevier B.V.