RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes
Tiantian Kou,
Lan Kang,
Bin Zhang,
Jiaqi Li,
Baohong Zhao,
Wenwen Zeng,
Xiaoyu Hu
Affiliations
Tiantian Kou
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China
Bin Zhang
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China
Jiaqi Li
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China
Arthritis and Tissue Degeneration Program and the David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, United States; Department of Medicine, Weill Cornell Medical College, New York, United States
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China
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.
