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Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

Abstract : 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-γ). Interleukin-10 (IL-10) inhibits IFN-γ 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-γ transcriptional signature, and we show that IFN-γ 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-γ production by these T cell subsets in vivo. Therefore, in addition to its established anti-inflammatory properties, IL-10 can induce IFN-γ production and EM, opening additional perspectives for the design of IL-10-based immunotherapies.
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Contributor : Marie-Christine Vougny Connect in order to contact the contributor
Submitted on : Wednesday, October 27, 2021 - 2:39:58 PM
Last modification on : Friday, August 5, 2022 - 12:02:58 PM


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Ana Cardoso, Ana Catarina Martins, Ana Raquel Maceiras, Wei Liu, Isabel Castro, et al.. Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis. Cell Reports, Elsevier Inc, 2021, 37 (4), pp.109887. ⟨10.1016/j.celrep.2021.109887⟩. ⟨pasteur-03405881⟩



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