G-CSF-treated granulocytes inhibit acute graft-versus-host disease

Vasconcelos, Zilton; Santos, B. M.; Farache, Júlia; Palmeira, Tereza S. S.; Areal, Rômulo B.; Cunha, José Marcos Telles da; Barcinski, Marcello A.; Bonomo, Adriana

doi:10.1182/blood-2005-08-3239

Cited by 32 publications

(38 citation statements)

References 48 publications

(54 reference statements)

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“…1) (24, 37). During tumor growth, increases of inflammation and tumor-derived factors, such as IL-1b (40), G-CSF (41,42), and IL-6 (39), might be responsible for these changes. Indeed, we observed that IL-6 levels in the sera were also increased with tumor growth (C.-Y.…”

Section: Discussionmentioning

confidence: 99%

Functional Changes in Myeloid-Derived Suppressor Cells (MDSCs) during Tumor Growth: FKBP51 Contributes to the Regulation of the Immunosuppressive Function of MDSCs

Kim

Lee

et al. 2012

The Journal of Immunology

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Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were downregulated but protumor function-related genes were upregulated in both monocytic MDSCs (Mo-MDSCs) and polymorphonuclear granulocytic MDSCs (PMN-MDSCs) at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo-MDSCs and PMN-MDSCs isolated from the late time points. Experiments using small interfering RNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing inducible NO synthase, arginase-1, and reactive oxygen species levels and enhancing NF-κB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs.

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Section: Discussionmentioning

confidence: 99%

Functional Changes in Myeloid-Derived Suppressor Cells (MDSCs) during Tumor Growth: FKBP51 Contributes to the Regulation of the Immunosuppressive Function of MDSCs

Kim

Lee

et al. 2012

The Journal of Immunology

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“…Apparently, the inhibition was due to oxidative stress created via the production of H 2 O 2 by activated PMN in vivo. A similar LDG phenotype could be induced by stimulating peripheral blood PMN in vitro [75,76], or in vivo [77]. These LDG recapitulate the tumour-induced PMN suppression of T lymphocyte cytokine synthesis via H 2 O 2 production.…”

Section: Pmn and T Cells In Tumoursmentioning

confidence: 91%

Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?

Müller

Munder

Kropf

et al. 2009

Trends in Immunology

243

206

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“…In this context, a recent report indicated that G-CSF treatment can induce low-density granulocytes, which inhibit acute graft-versus-host disease in mice. 43 We wondered whether the suppression mediated by tumorinduced MDSCs relied on the induction of T-cell anergy through an MHC-restricted presentation of antigen, as described by others. 4,6 By assessing the suppressive activity of MHC I-deficient or allogeneic MDSCs, this was shown to be unlikely in our in vitro cultures.…”

Section: Discussionmentioning

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

1,080

1,099

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G-CSF-treated granulocytes inhibit acute graft-versus-host disease

Cited by 32 publications

References 48 publications

Functional Changes in Myeloid-Derived Suppressor Cells (MDSCs) during Tumor Growth: FKBP51 Contributes to the Regulation of the Immunosuppressive Function of MDSCs

Functional Changes in Myeloid-Derived Suppressor Cells (MDSCs) during Tumor Growth: FKBP51 Contributes to the Regulation of the Immunosuppressive Function of MDSCs

Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms?

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

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