Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-gamma). Interleukin-10 (IL-10) inhibits IFN-gamma secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use 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-gamma transcriptional signature, and we show that IFN-gamma mediates IL-10-driven EM. We also find that IL-10, unexpectedly, reprograms CD4 and CD8 T cells toward an activation state that includes IFN-gamma production by these T cell subsets in vivo, Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-gamma production and EM, opening additional perspectives for the design of IL-10-based immunotherapies.

Automated summary

The study reveals that IL-10 triggers emergency myelopoiesis (EM) by expanding the myeloid progenitor compartment and production of myeloid cells. Unexpectedly, IL-10 also reprograms CD4 and CD8 T cells to produce IFN-gamma, suggesting new perspectives for IL-10-based immunotherapies.