RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes

Autor: Tiantian Kou, Lan Kang, Bin Zhang, Jiaqi Li, Baohong Zhao, Wenwen Zeng, Xiaoyu Hu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: eLife, Vol 12 (2024)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.88135
Popis: Notch-RBP-J signaling plays an essential role in the maintenance of myeloid homeostasis. However, its role in monocyte cell fate decisions is not fully understood. Here, we showed that conditional deletion of transcription factor RBP-J in myeloid cells resulted in marked accumulation of blood Ly6Clo monocytes that highly expressed chemokine receptor CCR2. Bone marrow transplantation and parabiosis experiments revealed a cell-intrinsic requirement of RBP-J for controlling blood Ly6CloCCR2hi monocytes. RBP-J-deficient Ly6Clo monocytes exhibited enhanced capacity competing with wildtype counterparts in blood circulation. In accordance with alterations of circulating monocytes, RBP-J deficiency led to markedly increased population of lung tissues with Ly6Clo monocytes and CD16.2+ interstitial macrophages. Furthermore, RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting Ccr2 in myeloid cells. These results demonstrate that RBP-J functions as a crucial regulator of blood Ly6Clo monocytes and thus derived lung-resident myeloid populations, at least in part through regulation of CCR2.
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