The role of CSF1R-dependent macrophages in control of the intestinal stem-cell niche.
The role of CSF1R-dependent macrophages in control of the intestinal stem-cell niche.
复制标题
DOI：
10.1038/s41467-018-03638-6
复制
发表时间：
2018-03-28
影响因子：
16.6
通讯作者：
Mabbott NA
中科院分区：
文献类型：
--
作者：
Sehgal A;Donaldson DS;Pridans C;Sauter KA;Hume DA;Mabbott NA
集落刺激因子1（CSF1）调控巨噬细胞的生长和分化，CSF1R信号通路参与肠道干细胞生态位的维持和潘氏细胞的分化，但CSF1R在肠腺中的表达尚不明确。在这里，我们表明，CSF1R依赖性巨噬细胞影响肠上皮分化和稳态。在肠固有层中，CSF1R mRNA表达仅限于与隐窝上皮密切相关的巨噬细胞，并且在潘氏细胞中检测不到。CSF1R阻断后的巨噬细胞消融影响潘氏细胞分化并导致Lgr5+肠干细胞减少。由巨噬细胞耗竭引起的对隐窝的干扰不利地影响肠上皮细胞谱系的后续分化。杯状细胞密度增加，而派尔集合淋巴结中M细胞的发育受阻。我们认为，在肠壁中的巨噬细胞的表型或丰度的修改改变了肠上皮细胞的发展和采样肠道抗原的能力。集落刺激因子1控制巨噬细胞的生长和分化。在这里，作者证明了其阻断耗尽肠道巨噬细胞并间接影响肠道上皮细胞分化，因为巨噬细胞有助于维持肠隐窝中的潘氏细胞和干细胞。
Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in the maintenance of the intestinal stem cell niche and differentiation of Paneth cells, but evidence of expression of CSF1R within the crypt is equivocal. Here we show that CSF1R-dependent macrophages influence intestinal epithelial differentiation and homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted to macrophages which are intimately associated with the crypt epithelium, and is undetectable in Paneth cells. Macrophage ablation following CSF1R blockade affects Paneth cell differentiation and leads to a reduction of Lgr5+ intestinal stem cells. The disturbances to the crypt caused by macrophage depletion adversely affect the subsequent differentiation of intestinal epithelial cell lineages. Goblet cell density is enhanced, whereas the development of M cells in Peyer’s patches is impeded. We suggest that modification of the phenotype or abundance of macrophages in the gut wall alters the development of the intestinal epithelium and the ability to sample gut antigens. Colony stimulating factor 1 controls the growth and differentiation of macrophages. Here the authors demonstrate that its blockade depletes gut macrophages and indirectly affects gut epithelial cell differentiation as the macrophages help maintain the Paneth and stem cells in intestinal crypts.
登录
查看更多内容
影响因子：
2.2
作者：
Inman, CF;Rees, LEN;Bailey, M
通讯作者：
Bailey, M
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.3
作者：
de Lau, Wim;Kujala, Pekka;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
29.4
作者：
Farin, Henner F.;Van Es, Johan H.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.