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Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.

ABSTRACT: Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.

SUBMITTER: Scott CL

PROVIDER: S-EPMC4737801 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.

Scott Charlotte L CL Zheng Fang F De Baetselier Patrick P Martens Liesbet L Saeys Yvan Y De Prijck Sofie S Lippens Saskia S Abels Chloé C Schoonooghe Steve S Raes Geert G Devoogdt Nick N Lambrecht Bart N BN Beschin Alain A Guilliams Martin M

Nature communications 20160127

Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-liv ...[more]

PMID: 26813785

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Project description:Classical CD16- vs intermediate/nonclassical CD16+ monocytes differ in their homing potential and biological functions, but whether they differentiate into dendritic cells (DCs) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify clinically relevant differences between CD16+ and CD16- monocyte-derived DCs (MDDCs). Although both CD16+ and CD16- MDDCs acquire classical immature/mature DC markers in vitro, genome-wide transcriptional profiling revealed unique molecular signatures for CD16+ MDDCs, including adhesion molecules (ITGAE/CD103), transcription factors (TCF7L2/TCF4), and enzymes (ALDH1A2/RALDH2), whereas CD16- MDDCs exhibit a CDH1/E-cadherin+ phenotype. Of note, lipopolysaccharides (LPS) upregulated distinct transcripts in CD16+ (eg, CCL8, SIGLEC1, MIR4439, SCIN, interleukin [IL]-7R, PLTP, tumor necrosis factor [TNF]) and CD16- MDDCs (eg, MMP10, MMP1, TGM2, IL-1A, TNFRSF11A, lysosomal-associated membrane protein 1, MMP8). Also, unique sets of HIV-modulated genes were identified in the 2 subsets. Further gene set enrichment analysis identified canonical pathways that pointed to "inflammation" as the major feature of CD16+ MDDCs at immature stage and on LPS/HIV exposure. Finally, functional validations and meta-analysis comparing the transcriptome of monocyte and MDDC subsets revealed that CD16+ vs CD16- monocytes preserved their superior ability to produce TNF-? and CCL22, as well as other sets of transcripts (eg, TCF4), during differentiation into DC. These results provide evidence that monocyte subsets are transcriptionally imprinted/programmed with specific differentiation fates, with intermediate/nonclassical CD16+ monocytes being precursors for pro-inflammatory CD103+RALDH2+TCF4+ DCs that may play key roles in mucosal immunity homeostasis/pathogenesis. Thus, alterations in the CD16+ /CD16- monocyte ratios during pathological conditions may dramatically influence the quality of MDDC-mediated immunity.

Dataset Information

Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.

Publications

Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.

Similar Datasets

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