The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells - Institut Pasteur Access content directly
Journal Articles Immunity Year : 2016

The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells

Thibaut Perchet
  • Function : Author
Elisa Gomez-Perdiguero
Rachel Golub
  • Function : Author

Abstract

Inflammation triggers the differentiation of Ly6C(hi) monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3(+)CD11c(-)MHCII(+)PU.1(hi) subset. This subset acted as a precursor for FcγRIII(+)PD-L2(+)CD209a(+), GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3(-)CD11c(-)MHCII(-)PU.1(lo) monocytes differentiated into FcγRIII(+)PD-L2(-)CD209a(-)iNOS(+) macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1(+/-) mice had reduced Flt3(+)CD11c(-)MHCII(+) monocytes and GM-CSF-dependent FcγRIII(+)PD-L2(+)CD209a(+) moDCs but generated iNOS(+) macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS(+) macrophages or moDCs.

Dates and versions

pasteur-01439253 , version 1 (18-01-2017)

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Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, et al.. The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells. Immunity, 2016, 45 (6), pp.1205 - 1218. ⟨10.1016/j.immuni.2016.12.001⟩. ⟨pasteur-01439253⟩
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