Osteocytes regulate neutrophil development through IL-19: a potent cytokine for neutropenia treatment

作者：Xiao, Min; Zhang, Wuju; Liu, Wen; Mao, Linlin; Yang, Jincheng; Hu, Le; Zhang, Sheng; Zheng, Yaling; Liu, Anling; Song, Qiancheng; Li, Yuhua; Xiao, Guozhi; Zou, Zhipeng^*; Bai, Xiaochun^*

来源：Blood, 2021, 137(25): 3533-3547.

DOI：10.1182/blood.2020007731

• COLONY-STIMULATING FACTOR
• HEMATOPOIETIC STEM
• FEBRILE NEUTROPENIA
• BONE-FORMATION
• GRANULOCYTE
• CELLS
• IL-20
• OSTEOCLASTOGENESIS
• INFLAMMATION
• METABOLISM

Osteocytes are the most abundant (90% to 95%) cells in bone and have emerged as an important regulator of hematopoiesis, but their role in neutrophil development and the underlying mechanisms remain unclear. Interleukin 19 (IL-19) produced predominantly by osteocytes stimulated granulopoiesis and neutrophil formation, which stimulated IL-19 receptor (IL-20R beta)/Stat3 signaling in neutrophil progenitors to promote their expansion and neutrophil formation. Mice with constitutive activation of mechanistic target of rapamycin complex (mTORC1) signaling in osteocytes (Dmp1-Cre) exhibited a dramatic increase in IL-19 production and promyelocyte/myelocytic expansion, whereas mTORC1 inactivation in osteocytes reduced IL-19 production and neutrophil numbers in mice. We showed that IL-19 administration stimulated neutrophil development, whereas neutralizing endogenous IL-19 or depletion of its receptor inhibited the process. Importantly, low-dose IL-19 reversed chemotherapy, irradiation, or chloramphenicol-induced neutropenia in mice more efficiently than granulocyte colony-stimulating factor. This evidence indicated that IL-19 was an essential regulator of neutrophil development and a potent cytokine for neutropenia treatment.

• 单位
  南方医科大学