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Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism.
Mucosal Immunology ( IF 8 ) Pub Date : 2019-Jan-01 , DOI: 10.1038/s41385-018-0096-2
Li-Yin Hung 1 , Debasish Sen 2 , Taylor K Oniskey 1 , Jeremey Katzen 3 , Noam A Cohen 4 , Andrew E Vaughan 5 , Wildaliz Nieves 1 , Anatoly Urisman 2 , Michael F Beers 3, 6 , Matthew F Krummel 2 , De'Broski R Herbert 1
Affiliation  

Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible for repair are poorly defined. This work demonstrates that lung macrophages rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, the presence of T, B, or ILC populations was not essential for macrophage-driven repair. Instead, conditional deletion of TFF2 in myeloid-restricted CD11cCre TFF2 flox mice exacerbated lung pathology and reduced the proliferative expansion of CD45- EpCAM+ pro-SPC+ alveolar type 2 cells. TFF2 deficient macrophages had reduced expression of the Wnt genes Wnt4 and Wnt16 and reconstitution of hookworm-infected CD11cCre TFF2flox mice with rWnt4 and rWnt16 restored the proliferative defect in lung epithelia post-injury. These data reveal a previously unrecognized mechanism wherein lung myeloid phagocytes utilize a TFF2/Wnt axis as a mechanism that drives epithelial proliferation following lung injury.

中文翻译:

巨噬细胞通过三叶因子 2 依赖机制促进感染性和非感染性肺损伤后的上皮细胞增殖。

巨噬细胞和上皮细胞之间的协调努力被认为对伤口愈合至关重要,但负责修复的巨噬细胞衍生分子定义不明确。这项工作表明,肺巨噬细胞依赖三叶因子 2 促进上皮细胞在无菌伤口、巴西日本圆线虫或硫酸博来霉素造成的损伤后增殖。出乎意料的是,T、B 或 ILC 群体的存在对于巨噬细胞驱动的修复并不是必不可少的。相反,在骨髓限制性 CD11c Cre TFF2 flox小鼠中条件性删除 TFF2 会加剧肺部病理并减少 CD45 - EpCAM + pro-SPC +的增殖性扩张肺泡2型细胞。TFF2 缺陷的巨噬细胞减少了 Wnt 基因 Wnt4 和 Wnt16 的表达,并且用 rWnt4 和 rWnt16 重建钩虫感染的 CD11c Cre TFF2 flox小鼠恢复了损伤后肺上皮细胞的增殖缺陷。这些数据揭示了一种以前未被认识的机制,其中肺髓样吞噬细胞利用 TFF2/Wnt 轴作为一种机制,在肺损伤后驱动上皮细胞增殖。
更新日期:2019-01-26
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