Evidence map›Paper›PMID 22942426›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction.

Gaetano Zizzo, Brendan A Hilliard, Marc Monestier, Philip L Cohen

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 398 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
398citing papers in PubMed, 2 pooled it
10.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

398 citing papers in PubMed, 2 syntheses or guidelines pooled it, 630 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. NLRC5-Deficient Macrophages Promote a Tumor-Permissive Phenotype via AXL- and MERTK-Mediated Efferocytosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Article
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  10. Advances in the study of macrophage polarization in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Review
  11. Article
  12. Article
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  14. Multifaceted regulation of immune cells in radiation-induced pulmonary fibrosis: from mechanistic insights to targeted therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  15. Article
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  17. Article
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338 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Gaetano ZizzoSection of Rheumatology, Department of Medicine, Temple University, Philadelphia, PA 19140, USA.
Brendan A Hilliard
Marc Monestier
Philip L Cohen
Temple University · US

Funding

Regulation of Immunity and Autoreactivity by the Mer Receptor Kinase SubfamilyU19AI082726 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI COHEN, PHILIP L · 2009 to 2013
$2.9M
Targeting TAM Receptors to Modulate Inflammation and AutoimmunityR21AI097758 · NIAID · TEMPLE UNIV OF THE COMMONWEALTH · PI COHEN, PHILIP L · 2012 to 2013
$421k
NIAID NIH HHS 5U19AI082726NIAID NIH HHS R21 AI097758NIAID NIH HHS U19 AI082726
6 · The paper itself

Abstract

Mer tyrosine kinase (MerTK) is a major macrophage apoptotic cell (AC) receptor. Its functional impairment promotes autoimmunity and atherosclerosis, whereas overexpression correlates with poor prognosis in cancer. However, little is known about mechanisms regulating MerTK expression in humans. We found that MerTK expression is heterogenous among macrophage subsets, being mostly restricted to anti-inflammatory M2c (CD14(+)CD16(+)CD163(+)CD204(+)CD206(+)CD209(-)) cells, differentiated by M-CSF or glucocorticoids. Small numbers of MerTK(+) "M2c-like" cells are also detectable among circulating CD14(bright)CD16(+) monocytes. MerTK expression levels adapt to changing immunologic environment, being suppressed in M1 and M2a macrophages and in dendritic cells. Remarkably, although glucocorticoid-induced differentiation is IL-10 independent, M-CSF-driven M2c polarization and related MerTK upregulation require IL-10. However, neither IL-10 alone nor TGF-β are sufficient to fully differentiate M2c (CD16(+)CD163(+)MerTK(+)) macrophages. M-CSF and IL-10, both released by T lymphocytes, may thus be required together to promote regulatory T cell-mediated induction of anti-inflammatory monocytes-macrophages. MerTK enables M2c macrophages to clear early ACs more efficiently than other macrophage subsets, and it mediates AC clearance by CD14(bright)CD16(+) monocytes. Moreover, M2c cells release Gas6, which in turn amplifies IL-10 secretion via MerTK. IL-10-dependent induction of the Gas6/MerTK pathway may, therefore, constitute a positive loop for M2c macrophage homeostasis and a critical checkpoint for maintenance of anti-inflammatory conditions. Our findings give new insight into human macrophage polarization and favor a central role for MerTK in regulation of macrophage functions. Eliciting M2c polarization can have therapeutic utility for diseases such as lupus, in which a defective AC clearance contributes to initiate and perpetuate the pathological process.

Indexed as

ApoptosisAutocrine CommunicationCell DifferentiationCell MovementCell PolarityCells, Culturedc-Mer Tyrosine KinaseDendritic CellsHumansImmunophenotypingMacrophagesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesTranscriptional Activationc-Mer Tyrosine KinaseMERTK protein, humanProto-Oncogene ProteinsReceptor Protein-Tyrosine Kinases

Identifiers

PMID22942426
PMCPMC3465703
OpenAlexW2144741217

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.