| Literature DB >> 33684929 |
Min Xiao1,2, Wuju Zhang1,2, Wen Liu2, Linlin Mao1, Jincheng Yang3, Le Hu1, Sheng Zhang2, Yaling Zheng4, Anling Liu1, Qiancheng Song1, Yuhua Li4, Guozhi Xiao5, Zhipeng Zou2, Xiaochun Bai1,2,6.
Abstract
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-20Rβ)/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.Entities:
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Year: 2021 PMID： 33684929 PMCID： PMC8225922 DOI： 10.1182/blood.2020007731
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113