Peroxisome proliferator-activated receptor γ (PPARγ) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer

Ginderachter, Jo A. Van; Meerschaut, Sofie; Liu, Yuanqing; Brys, Lea; Groeve, Kurt De; Ghassabeh, Gholamreza Hassanzadeh; Raes, Geert; Baetseĺier, Patrick De

doi:10.1182/blood-2005-09-3777

Cited by 106 publications

(107 citation statements)

References 69 publications

(100 reference statements)

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…35,38,39 As demonstrated by our studies and those of others, syngeneic CD4 1 CD25 1 Tregs have been shown to be critical for the induction of the macrophage phenotype switch both in vivo and in vitro. 14,15 In this study, the allogeneic donor CD4 1 CD25 1 Tregs caused significant phenotypic and functional alterations of the resident macrophages in the recipient NOD-scid mice to an M2-like phenotype.…”

Section: Discussionsupporting

confidence: 68%

“…CD4 1 T responders (2310 5 ) and macrophage stimulators (1310 5 ), which were pre-treated with 50 mg/mL mitomycin C, were incubated in triplicate in 0.2 mL medium in Ubottomed 96-well microplates (Costar) at 37 uC in 5% CO 2 . 18,28,34,35 The plates were pulsed with 1 mCi of 3 H-labeled thymidine (radioactivity, 185 GBq/mM; Atomic Energy Research Establishment, Beijing, China) per well on day 3, and after 18 h of further incubation, the cells were harvested onto glass fiber filters with an automatic cell harvester (Tomtec, Toku, Finland). The samples were assayed in a .…”

Section: Detection Of Ifn-c Il-4 and Il-10mentioning

confidence: 99%

See 1 more Smart Citation

Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells

Liu

Hou

et al. 2012

Cell Mol Immunol

View full text Add to dashboard Cite

CD4 1 CD25 1 regulatory T cells (Tregs) play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4 1 CD25 1 Tregs can regulate recipient mouse macrophages is unknown. The effect of allogeneic donor CD4 1 CD25 1 Tregs on recipient mouse resident F4/80 1 macrophages was investigated using a mouse model in which allogeneic donor CD4 1 CD25 1 Tregs were adoptively transferred into the peritoneal cavity of host NOD-scid mice. The phenotype and function of the recipient macrophages were then assayed. The peritoneal F4/80 1 macrophages in the recipient mice that received the allogeneic CD4 1 CD25 1 Tregs expressed significantly higher levels of CD23 and programmed cell death-ligand 1(PD-L1) and lower levels of CD80, CD86, CD40 and MHC II molecules compared to the mice that received either allogeneic CD4 1 CD25 2 T cells (Teffs) or no cells. The resident F4/80 1 macrophages of the recipient mice injected with the allogeneic donor CD4 1 CD25 1 Tregs displayed significantly increased phagocytosis of chicken red blood cells (cRBCs) and arginase activity together with increased IL-10 production, whereas these macrophages also showed decreased immunogenicity and nitric oxide (NO) production. Blocking arginase partially but significantly reversed the effects of CD4 1 CD25 1 Tregs with regard to the induction of the M2 macrophages in vivo. Therefore, the allogeneic donor CD4 1 CD25 1 Tregs can induce the M2 macrophages in recipient mice at least in part via an arginase pathway. We have provided in vivo evidence to support the unknown pathways by which allogeneic donor CD4 1 CD25 1 Tregs regulate innate immunity in recipient mice by promoting the differentiation of M2 macrophages.

show abstract

Section: Discussionsupporting

confidence: 68%

Section: Detection Of Ifn-c Il-4 and Il-10mentioning

confidence: 99%

Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells

Liu

Hou

et al. 2012

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…Tumor dissociation was performed as described earlier. 12 Fluorescence-activated cell sorting (FACS) data were acquired using a FACSVantage SE flow cytometer or FACS Canto 2 (BD Biosciences).…”

Section: Fluorescence-activated Cell Sorting Staining and Flow Cytometrymentioning

confidence: 99%

“…Despite this notion, these cells are typically studied as a bulk population and only a few reports have addressed a further refinement of this population. 3,8,12 It has been suggested that different tumor-derived factors, such as granulocyte macrophage-colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), IL-1␤, and prostaglandins, can mobilize MDSC recruitment from bone marrow hematopoietic precursors and induce the immunosuppressive phenotype. [13][14][15][16][17][18] While this immunosuppressive phenotype is a trademark of MDSCs, there is no clear consensus on their suppressive mechanism.…”

Section: Introductionmentioning

confidence: 99%

Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell–suppressive activity

Movahedi

Guilliams

Bossche

et al. 2008

Blood

Self Cite

1,095

1,102

View full text Add to dashboard Cite

“…Decreased NF-B signaling is likely to be responsible for the impaired expression of M1 genes, as overexpression of the p50 NF-B subunit, which lacks a strong transactivation domain, is sufficient to repress M1 gene expression (6). The ability of macrophages to suppress cytotoxic T lymphocyte activity is also impaired by activation of PPAR␥ (7), indicating that in this context PPAR␥ activation suppresses M2 polarization. However, the role of PPAR␥ remains controversial, as PPAR␥ activation has been observed to promote M2 polarization in adipose tissue (8).…”

mentioning

confidence: 99%

A CREB-C/EBPβ cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair

Ruffell

Mourkioti²,

Gambardella³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

542

439

View full text Add to dashboard Cite

Macrophages play an essential role in the resolution of tissue damage through removal of necrotic cells, thus paving the way for tissue regeneration. Macrophages also directly support the formation of new tissue to replace the injury, through their acquisition of an anti-inflammatory, or M2, phenotype, characterized by a gene expression program that includes IL-10, the IL-13 receptor, and arginase 1. We report that deletion of two CREB-binding sites from the Cebpb promoter abrogates Cebpb induction upon macrophage activation. This blocks the downstream induction of M2-specific Msr1, Il10, II13ra, and Arg-1 genes, whereas the inflammatory (M1) genes Il1, Il6, Tnfa, and Il12 are not affected. Mice carrying the mutated Cebpb promoter (␤⌬Cre) remove necrotic tissue from injured muscle, but exhibit severe defects in muscle fiber regeneration. Conditional deletion of the Cebpb gene in muscle cells does not affect regeneration, showing that the C/EBP␤ cascade leading to muscle repair is muscle-extrinsic. While ␤⌬Cre macrophages efficiently infiltrate injured muscle they fail to upregulate Cebpb, leading to decreased Arg-1 expression. CREB-mediated induction of Cebpb expression is therefore required in infiltrating macrophages for upregulation of M2-specific genes and muscle regeneration, providing a direct genetic link between these two processes.macrophage polarization ͉ muscle regeneration ͉ transcription

show abstract

Peroxisome proliferator-activated receptor γ (PPARγ) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer

Cited by 106 publications

References 69 publications

Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells

Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells

Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell–suppressive activity

A CREB-C/EBPβ cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair

Contact Info

Product

Resources

About