Treatment With Granulocyte Colony−Stimulating Factor Prevents Diabetes in NOD Mice by Recruiting Plasmacytoid Dendritic Cells and Functional CD4+CD25+ Regulatory T-Cells

Kared, Hassen; Masson, Annie; Adle‐Biassette, Homa; Bach, Jean‐François; Chatenoud, Lucienne; Zavala, Flora

doi:10.2337/diabetes.54.1.78

Cited by 122 publications

(102 citation statements)

References 51 publications

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“…G-CSF induces an immunoregulatory shift from a T-helper type 1 to a T-helper type 2 cytokine phenotype, increases tolerogenic dendritic cells and mobilises regulatory T cells [12][13][14]. G-CSF has successfully prevented both the onset of disease in the NOD mouse and cyclophosphamide-mediated acceleration of diabetes [15,16]. Parker et al have recently shown that G-CSF enhances the long-term reversal of diabetes afforded by murine antithymocyte globulin (ATG) [4].…”

Section: Introductionmentioning

confidence: 99%

Intradermal α1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease

et al. 2010

Diabetologia

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Aims/hypothesis Human α1-antitrypsin (hAAT) gene therapy prevents type 1 diabetes in a NOD mouse model of diabetes. However, repeated i.p. injections of hAAT into NOD mice leads to fatal anaphylaxis. The aim of the study was to determine if an alternative route of administration avoids anaphylaxis and allows evaluation of hAAT's potential for diabetes prevention and reversal. We also sought to determine if the addition of granulocyte colonystimulating factor (G-CSF), augments hAAT's capacity to prevent or reverse disease in the NOD mice. Methods To evaluate hAAT pharmacokinetics, serum hAAT levels were monitored in NOD mice receiving a single dose (2 mg) of hAAT by i.p., s.c. or i.d. injection.

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Section: Introductionmentioning

confidence: 99%

Intradermal α1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease

et al. 2010

Diabetologia

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“…The hematopoietic growth factor G-CSF prevented T1D in NOD mice if administrated during consecutive 5 d every 4 wk at 4,8,12, and 16 wk of age (5). This treatment promoted the recruitment to the pancreatic lymph nodes (PLN) of Tregs, which play a key role in the protection against T1D conferred by G-CSF.…”

mentioning

confidence: 99%

“…These data assign a key role to CD8a Interestingly, some biological agents already used in the clinics for other applications display such properties. Thus, treatment with G-CSF provides protection against various experimental autoimmune diseases, including lupus nephritis, experimental autoimmune encephalomyelitis, colitis, and type 1 diabetes (T1D) (1)(2)(3)(4)(5). T1D is an autoimmune disease characterized by the infiltration in the pancreatic islets of autoreactive T cells that target insulinproducing b cells.…”

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confidence: 99%

CCL22-Producing CD8α− Myeloid Dendritic Cells Mediate Regulatory T Cell Recruitment in Response to G-CSF Treatment

Layseca-Espinosa

Korniotis

Montandon

et al. 2013

The Journal of Immunology

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G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local recruitment of T regulatory cells (Tregs). This is an indirect effect because adoptive transfer of G-CSF–induced tolerogenic dendritic cells (DCs) promotes Treg accumulation. However, the identity of the particular DC subset and the molecule(s) mediating this effect remain unknown. We demonstrate in this study that the adoptive transfer of CD11chighCD8α− DCs isolated from pegylated G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the pancreatic recruitment of CD4+CD25+Foxp3+ Tregs, which generated increased amounts of TGF-β. Likewise, only CD11chighCD8α− DCs from pegG-CSF recipients secreted the chemokine CCL22 at levels that effectively attracted Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by CD11chighCD8α− DCs from the pancreatic lymph nodes compared with those from the spleen. Accordingly, CD11chighCD8α− DCs from the pancreatic lymph nodes of pegG-CSF recipients were more efficient than their splenic counterparts in the recruitment of Tregs upon adoptive transfer. Predictably, CD11chighCD8α− DCs failed to recruit these Tregs both in vivo and in vitro following intracellular neutralization of CCL22. These data assign a key role to CD8α− DCs and CCL22 in Treg recruitment in the protection of NOD mice against type 1 diabetes following the treatment with G-CSF.

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“…G-CSF inhibits onset of diabetes in the cyclophosphamide-accelerated mouse model [43] and prevents beta cell destruction [44]. G-CSF and GM-CSF prevent onset of diabetes in NOD mice by inducing tolerogenic dendritic cells that sustain the function of regulatory T cells [45,46]. It is possible that production of GM-CSF and G-CSF contributes to the observed positive correlation between the number of ductal cells in islets graft and the outcome of the transplantation [47].…”

Section: Discussionmentioning

confidence: 99%

CD40 activation in human pancreatic islets and ductal cells

et al. 2008

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Aims/hypothesis CD40 expression on non-haematopoietic cells is linked to inflammation. We previously reported that CD40 is expressed on isolated human and non-human primate islets and its activation results in secretion of IL-8, macrophage inflammatory protein 1-beta (MIP-1β) and monocyte chemoattractant protein-1 (MCP-1) through nuclear factor-κB and extracellularly regulated kinases 1/2 pathways. The objective of this study was to identify the pattern of gene expression, and to study viability and functionality affected by CD40-CD40 ligand (CD40L) interaction in human islets. Furthermore, we have studied the CD40-mediated cytokine/chemokine profile in pancreatic ductal cells, as they are always present in human islet transplant preparations and express CD40 constitutively. Methods CD40-CD40L gene expression modulation was studied by microarray on islet cells depleted of ductal cells. Selected genes were validated by quantitative RT-PCR. The cytokine profile in purified ductal cells was evaluated by Luminex technology, based on the use of fluorescent-coated beads, known as microspheres, and capable of multiplex detection of proteins from a single sample. Glucosestimulated insulin secretion and islet viability were assessed by perifusion and 7-aminoactinomycin D membrane exclusion, respectively. Results Statistical analysis of microarrays identified 30 genes exhibiting at least a 2.5-fold increase across all replicate arrays. The majority of them were related to oxidative stress/inflammation. Prominently upregulated were chemokine C-X-C motif ligand 1 (CXCL1), CXCL2and CXCL3 belonging to the CXC family of chemokines related to IL-8. CD40-mediated CXCL1 secretion was confirmed by ELISA. The viability or in vitro function was not affected by CD40 activation. In addition to previously reported IL-8, MIP-1β and MCP-1, CD40 stimulation in ductal cells produced IL-1β, IFN-γ, TNF-α, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Conclusions/interpretation CD40 activation in islets and ductal cells produces cytokines/chemokines with a broadspectrum range of biological functions.

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Treatment With Granulocyte Colony−Stimulating Factor Prevents Diabetes in NOD Mice by Recruiting Plasmacytoid Dendritic Cells and Functional CD4+CD25+ Regulatory T-Cells

Cited by 122 publications

References 51 publications

Intradermal α1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease

Intradermal α1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease

CCL22-Producing CD8α− Myeloid Dendritic Cells Mediate Regulatory T Cell Recruitment in Response to G-CSF Treatment

CD40 activation in human pancreatic islets and ductal cells

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