| First Author | Li Y | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 6 | Pages | 1434-1444 |
| PubMed ID | 35246496 | Mgi Jnum | J:322726 |
| Mgi Id | MGI:7257987 | Doi | 10.4049/jimmunol.2100878 |
| Citation | Li Y, et al. (2022) Protein Tyrosine Phosphatase PTPRO Signaling Couples Metabolic States to Control the Development of Granulocyte Progenitor Cells. J Immunol 208(6):1434-1444 |
| abstractText | Protein tyrosine phosphatase (PTPase) is critically involved in the regulation of hematopoietic stem cell development and differentiation. Roles of novel isolated receptor PTPase PTPRO from bone marrow hematopoietic stem cells in granulopoiesis have not been investigated. PTPRO expression is correlated with granulocytic differentiation, and Ptpro (-/-) mice developed neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors under steady-state and potentiated innate immune responses against Listeria monocytogenes infection. Mechanistically, mTOR and HIF1alpha signaling engaged glucose metabolism and initiated a transcriptional program involving the lineage decision factor C/EBPalpha, which is critically required for the PTPRO deficiency-directed granulopoiesis. Genetic ablation of mTOR or HIF1alpha or perturbation of glucose metabolism suppresses progenitor expansion, neutrophilia, and higher glycolytic activities by Ptpro (-/-) In addition, Ptpro (-/-) upregulated HIF1alpha regulates the lineage decision factor C/EBPalpha promoter activities. Thus, our findings identify a previously unrecognized interplay between receptor PTPase PTPRO signaling and mTOR-HIF1alpha metabolic reprogramming in progenitor cells of granulocytes that underlies granulopoiesis. |
