Transcript profiling of <scp>CD</scp>16‐positive monocytes reveals a unique molecular fingerprint

Frankenberger, Marion; Hofer, Thomas P.; Marei, Ayman; Dayyani, Farshid; Schewe, Stefan; Strasser, Christine; Aldraihim, Asaad; Stanzel, Franz; Lang, Roland; Hoffmann, Reinhard; Costa, Olivia Prazeres da; Buch, Thorsten; Ziegler-Heitbrock, Loems

doi:10.1002/eji.201141907

Cited by 87 publications

(74 citation statements)

References 30 publications

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“…In a previous study, Frankenberger et al (44) reported that M16 expressed a lower level of CD14 and CD163 transcripts with respect to M14. In the present study, we corroborate that the expression of key phenotypic markers of MMfs (CD14, CD163, CD209, and FRb) (29) is greatly diminished in M16, whereas they abundantly express the GM-CSF-associated marker CLEC5A (34).…”

Section: Discussionmentioning

confidence: 91%

Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages

González-Domínguez

Domínguez-Soto

Nieto

et al. 2016

The Journal of Immunology

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Human CD14++CD16− and CD14+/loCD16+ monocyte subsets comprise 85 and 15% of blood monocytes, respectively, and are thought to represent distinct stages in the monocyte differentiation pathway. However, the differentiation fates of both monocyte subsets along the macrophage (Mϕ) lineage have not yet been elucidated. We have now evaluated the potential of CD14++ CD16− and CD16+ monocytes to differentiate and to be primed toward pro- or anti-inflammatory Mϕs upon culture with GM-CSF or M-CSF, respectively (subsequently referred to as GM14, M14, GM16, or M16). Whereas GM16 and GM14 were phenotypic and functionally analogous, M16 displayed a more proinflammatory profile than did M14. Transcriptomic analyses evidenced that genes associated with M-CSF–driven Mϕ differentiation (including FOLR2, IL10, IGF1, and SERPINB2) are underrepresented in M16 with respect to M14. The preferential proinflammatory skewing of M16 relative to M14 was found to be mediated by the secretion of activin A and the low levels of IL-10 produced by M16. In fact, activin A receptor blockade during the M-CSF–driven differentiation of CD16+ monocytes, or addition of IL-10–containing M14-conditioned medium, significantly enhanced their expression of anti-inflammatory–associated molecules while impairing their acquisition of proinflammatory-related markers. Thus, we propose that M-CSF drives CD14++CD16ˉ monocyte differentiation into bona fide anti-inflammatory Mϕs in a self-autonomous manner, whereas M-CSF–treated CD16+ monocytes generate Mϕs with a skewed proinflammatory profile by virtue of their high activin A expression unless additional anti-inflammatory stimuli such as IL-10 are provided.

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Section: Discussionmentioning

confidence: 91%

Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages

González-Domínguez

Domínguez-Soto

Nieto

et al. 2016

The Journal of Immunology

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“…[SAGE]) technologies. 11,12,28,29 For the present study, we have used the highly sensitive MACE approach for determination of the transcriptome. 22 When comparing the present results to the previous SuperSAGE approach, 11 we found a similar gene expression pattern for monocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

“…15 It has clearly been shown previously that the CD16-positive monocytes cocluster with monocytes and not with DCs. 29,32,33 Still, one could hypothesize that the slan-positive subset of the CD16-positive monocytes might have a gene expression pattern matching that of DCs. Evidence supporting the concept that slan-positive cells and DCs are distinct has been published earlier, in that TLR3, -4 and -10 transcripts did show a reciprocal expression pattern in slan-positive cells and DCs.…”

Section: Discussionmentioning

confidence: 99%

slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation

Hofer

Zawada

Frankenberger

et al. 2015

Blood

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112

116

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“…Notably, the CD16 + subset accounts for only 10% of the total monocyte population in healthy donors, displaying a unique cell-surface marker expression and cytokine secretion pattern in comparison with its CD16 − counterpart [13,14]. Indeed, upon stimulation with lipopolysaccharide, CD16 + monocytes isolated from healthy donors secrete higher amounts of pro-inflammatory factors such as tumor necrosis factor-alpha (TNFα), interleukin-1-beta (IL-1) and IL-6, but low amount of the anti-inflammatory mediator IL-10 [13,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

et al. 2015

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The human CD14 + monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16 + monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16 + CD163 + MerTK + pSTAT3 + phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16 + CD163 + MerTK + pSTAT3 + cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16 + C-D163 + MerTK + pSTAT3 + monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy.

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Transcript profiling of CD16‐positive monocytes reveals a unique molecular fingerprint

Abstract: CD16-positive (CD14 ++CD16

Cited by 87 publications

References 30 publications

Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages

Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages

slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

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