Interleukin-10 causes interferon ?-dependent emergency myelopoiesis

In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production is observed, often mediated by the pro-inflammatory cytokine IFN-?. IL-10 inhibits IFN-? secretion, largely by its effects on macrophages and dendritic cells, but, paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work we used different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells. Hematopoietic progenitors display a prominent IFN-? transcriptional signature, and we show that IFN-? mediates IL-10-driven EM. We also found that IL-10, unexpectedly, induces IFN-? production by all T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-? production and EM, opening new perspectives for the design of IL-10-based immunotherapies. Overall design: AmpliSeq Transcriptome was performed in sorted bone marrow CD4 and CD8 T cells from three pMT-10 overexpressing IL-10, three C57BL/6 (control), and three control pMT-10.