Type I IFN drives emergency myelopoiesis during chronic and acute TLR7 signaling and acute viral infection (P4478)
| Autor: | Jessica Hamerman, Matthew Buechler, Daniel Campbell, Thomas Teal, Keith Elkon |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:52.56-52.56 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Mice overexpressing TLR7 (TLR7.1 mice) are a model of systemic lupus erythematosus pathogenesis and exhibit peripheral myeloid expansion. We show that TLR7.1 mice have a dramatic expansion of splenic cells that derive from granulocyte/macrophage progenitors (GMP) compared with wild-type mice. In the bone marrow, TLR7.1 mice exhibited hallmarks of emergency myelopoiesis and contained a discrete population of Sca-1+ GMP, termed emergency GMP (eGMP). The emergency myelopoiesis and peripheral myeloid expansion in TLR7.1 mice was dependent on type I IFN signaling. eGMP were found in a type I IFN-dependent manner during both acute and chronic TLR7 agonist administration and during acute LCMV infection. Using in vitro colony forming unit assays, we found that eGMP are superior myeloid precursors than GMP. In vivo, eGMP turnover more than GMP, suggesting that the superiority of eGMP to generate myeloid cells in vitro may stem from their increased ability to proliferate. This study shows that type I IFN can act upon myeloid progenitors to promote the development of emergency GMP, which leads to an expansion of their progeny in the periphery. Further studies are underway to understand the molecular mechanisms that differentiate eGMP from GMP and other myeloid progenitor cells. |
| Databáze: | OpenAIRE |
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