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Expression data from a variant monocyte population following dendritc cell depletion

ABSTRACT: Ly6C+ ‘classical’ monocytes respond rapidly to inflammation, either directly as effector cells or by differentiating into inflammatory macrophages and dendritic cells (DC). In the absence of DC, elevated levels of serum Flt3L and G-CSF induce a monocytosis although the properties of this expanded population have not been addressed. Here, we show that depletion of DC using the CD11c-DTR model results in rapid and CCR2-independent expansion of a variant population of splenic MHC Class II+ CD64+ Ly6C+ monocytes that are distinct from both circulating blood Ly6C+ monocytes and their tissue counterparts, but resemble Ly6C+ cells mobilized by exogenous G-CSF and Flt3L. The CD64+ Ly6C+ monocyte population is characterized by up-regulation of TLR signalling apparatus and an increased capacity to produce TNF-a following stimulation. Therefore, perturbation within the mononuclear phagocytic system in the absence of inflammation induces an alternative differentiation pathway that drives expansion of monocytes poised for innate immune activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE58263 | GEO | 2015/04/01

SECONDARY ACCESSION(S): PRJNA251796

REPOSITORIES: GEO

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Expression data from a variant monocyte population following dendritc cell depletion

Project description:Ly6C+ ‘classical’ monocytes respond rapidly to inflammation, either directly as effector cells or by differentiating into inflammatory macrophages and dendritic cells (DC). In the absence of DC, elevated levels of serum Flt3L and G-CSF induce a monocytosis although the properties of this expanded population have not been addressed. Here, we show that depletion of DC using the CD11c-DTR model results in rapid and CCR2-independent expansion of a variant population of splenic MHC Class II+ CD64+ Ly6C+ monocytes that are distinct from both circulating blood Ly6C+ monocytes and their tissue counterparts, but resemble Ly6C+ cells mobilized by exogenous G-CSF and Flt3L. The CD64+ Ly6C+ monocyte population is characterized by up-regulation of TLR signalling apparatus and an increased capacity to produce TNF-a following stimulation. Therefore, perturbation within the mononuclear phagocytic system in the absence of inflammation induces an alternative differentiation pathway that drives expansion of monocytes poised for innate immune activation. Monocytes populations were purified from CD11c-DTR mice which were injected with PBS or diphtheria toxin 48 hours previously. Common monocyte progenitors (cMoP) were isolated from untreated C57BL/6 mice. 48 hours after injection of PBS or DT, monocytes were purified from the spleen after collagenase digestion and flow sorted directly into Qiagen RLT buffer. cMoP were purified directly from the bone marrow without digestion enzymes.

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