Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.
Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.
复制标题
DOI：
10.1038/ni.3734
复制
发表时间：
2017-06
影响因子：
30.5
通讯作者：
Loke P
中科院分区：
文献类型：
--
作者：
Gundra UM;Girgis NM;Gonzalez MA;San Tang M;Van Der Zande HJP;Lin JD;Ouimet M;Ma LJ;Poles J;Vozhilla N;Fisher EA;Moore KJ;Loke P
激活的炎性巨噬细胞是否可以采用组织驻留巨噬细胞的特征，以及介导这种表型转换的机制尚不清楚。在此，我们发现，在小鼠的腹膜腔和感染曼氏血吸虫的小鼠肝脏肉芽肿形成过程中，需要维生素A将白介素4(IL-4)激活的单核细胞衍生的F4/80intCD206+PD-L2+MHCII+巨噬细胞表型转化为组织驻留F4/80hiCD206−PD-L2−MHCII−UCP1+表型的巨噬细胞。F4/80intCD206+巨噬细胞向F4/80hiCD206−巨噬细胞的表型转换与染色质景观的几乎完全重塑以及转录谱的改变有关。感染曼氏血吸虫的维生素A缺乏小鼠肝脏肉芽肿构筑被破坏，死亡率增加，提示在蠕虫感染过程中，不能将F4/80intCD206+巨噬细胞转化为F4/80hiCD206−巨噬细胞可能导致炎症调节失调。
Whether activated inflammatory macrophages can adopt features of tissue resident macrophages and what mechanisms mediate this phenotypic conversion remain unclear. Here we show that vitamin A was required for phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80intCD206+PD-L2+MHCII+ macrophages into macrophages with a tissue-resident F4/80hiCD206−PD-L2−MHCII−UCP1+ phenotype in the peritoneal cavity of mice and during liver granuloma formation in mice infected with Schistosoma mansoni. Phenotypic conversion of F4/80intCD206+ macrophages into F4/80hiCD206− macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A deficient mice infected with S. mansoni had disrupted liver granuloma architecture and increased mortality, indicating that failure to convert from F4/80intCD206+ macrophages to F4/80hiCD206− macrophages may lead to dysregulated inflammation during helminth infection.