Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis - Institut Pasteur Access content directly
Journal Articles Cell Reports Year : 2021

Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

Wei Liu
James Di Santo
Yan Li

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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Immunology
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Dates and versions

pasteur-03405881 , version 1 (27-10-2021)

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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, 2021, 37 (4), pp.109887. ⟨10.1016/j.celrep.2021.109887⟩. ⟨pasteur-03405881⟩

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