HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kared, H. Articles by Zavala, F. Search for Related Content PubMed PubMed Citation Articles by Kared, H. Articles by Zavala, F. Social Bookmarking                What's this?

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

¹ National Institute of Health and Medical Research, INSERM U580, Necker Enfants Malades Research Institute, Hôpital Necker, Paris, France
² Pathology Laboratory, Bichat-Claude Bernard Hospital, Assistance Publique Hôpitaux de Paris, Paris, France

Accumulating evidence that granulocyte colony–stimulating factor (G-CSF), the key hematopoietic growth factor of the myeloid lineage, not only represents a major component of the endogenous response to infections, but also affects adaptive immune responses, prompted us to investigate the therapeutic potential of G-CSF in autoimmune type 1 diabetes. Treatment with G-CSF protected NOD mice from developing spontaneous diabetes. G-CSF triggered marked recruitment of dendritic cells (DCs), particularly immature CD11c^loB220⁺ plasmacytoid DCs, with reduced costimulatory signal expression and higher interferon- but lower interleukin-12p70 release capacity than DCs in excipient-treated mice. G-CSF recipients further displayed accumulation of functional CD4⁺CD25⁺ regulatory T-cells that produce transforming growth factor-ß1 (TGF-ß1) and actively suppressed diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. G-CSF’s ability to promote key tolerogenic interactions between DCs and regulatory T-cells was demonstrated by enhanced recruitment of TGF-ß1–expressing CD4⁺CD25⁺ cells after adoptive transfer of DCs isolated from G-CSF– relative to vehicle-treated mice into naive NOD recipients. The present results suggest that G-CSF, a promoter of tolerogenic DCs, may be evaluated for the treatment of human type 1 diabetes, possibly in association with direct inhibitors of T-cell activation. They also provide a rationale for a protective role of the endogenous G-CSF produced during infections in early diabetes.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Huang, I. J. Fugier-Vivier, T. Miller, M. J. Elliott, H. Xu, L. D. Bozulic, P. M. Chilton, and S. T. Ildstad Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis? Diabetes, September 1, 2008; 57(9): 2360 - 2370. [Abstract] [Full Text] [PDF]

				S. Gaudreau, C. Guindi, M. Menard, G. Besin, G. Dupuis, and A. Amrani Granulocyte-Macrophage Colony-Stimulating Factor Prevents Diabetes Development in NOD Mice by Inducing Tolerogenic Dendritic Cells that Sustain the Suppressive Function of CD4+CD25+ Regulatory T Cells J. Immunol., September 15, 2007; 179(6): 3638 - 3647. [Abstract] [Full Text] [PDF]

				B. J. E. Raveney and D. J. Morgan Dynamic Control of Self-Specific CD8+ T Cell Responses via a Combination of Signals Mediated by Dendritic Cells J. Immunol., September 1, 2007; 179(5): 2870 - 2879. [Abstract] [Full Text] [PDF]

				U. Bharadwaj, M. Li, R. Zhang, C. Chen, and Q. Yao Elevated Interleukin-6 and G-CSF in Human Pancreatic Cancer Cell Conditioned Medium Suppress Dendritic Cell Differentiation and Activation Cancer Res., June 1, 2007; 67(11): 5479 - 5488. [Abstract] [Full Text] [PDF]

				S. Brode, T. Raine, P. Zaccone, and A. Cooke Cyclophosphamide-Induced Type-1 Diabetes in the NOD Mouse Is Associated with a Reduction of CD4+CD25+Foxp3+ Regulatory T Cells J. Immunol., November 15, 2006; 177(10): 6603 - 6612. [Abstract] [Full Text] [PDF]

				S. Rutella, S. Danese, and G. Leone Tolerogenic dendritic cells: cytokine modulation comes of age Blood, September 1, 2006; 108(5): 1435 - 1440. [Abstract] [Full Text] [PDF]

				M. Condomines, P. Quittet, Z.-Y. Lu, L. Nadal, P. Latry, E. Lopez, M. Baudard, G. Requirand, C. Duperray, J.-F. Schved, et al. Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor. J. Immunol., June 1, 2006; 176(11): 6631 - 6639. [Abstract] [Full Text] [PDF]

				E. S. Morris, K. P. A. MacDonald, and G. R. Hill Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood, May 1, 2006; 107(9): 3430 - 3435. [Abstract] [Full Text] [PDF]

				C. Teuscher, R. W. Doerge, P. D. Fillmore, and E. P. Blankenhorn eae36, a Locus on Mouse Chromosome 4, Controls Susceptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter Genetics, February 1, 2006; 172(2): 1147 - 1153. [Abstract] [Full Text] [PDF]

				S. Rutella, F. Zavala, S. Danese, H. Kared, and G. Leone Granulocyte Colony-Stimulating Factor: A Novel Mediator of T Cell Tolerance J. Immunol., December 1, 2005; 175(11): 7085 - 7091. [Abstract] [Full Text] [PDF]