| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892
In this study we show that activation of STAT pathways is developmentally regulated and plays a role in dendritic cell (DC) differentiation and maturation. The STAT6 signaling pathway is constitutively activated in immature DC (iDC) and declines as iDCs differentiate into mature DCs (mDCs). However, down-regulation of this pathway during DC differentiation is accompanied by dramatic induction of suppressors of cytokine signaling 1 (SOCS1), SOCS2, SOCS3, and cytokine-induced Src homology 2-containing protein expression, suggesting that inhibition of STAT6 signaling may be required for DC maturation. In contrast, STAT1 signaling is most robust in mDCs and is not inhibited by the up-regulated SOCS proteins, indicating that STAT1 and STAT6 pathways are distinctly regulated in maturing DC. Furthermore, optimal activation of STAT1 during DC maturation requires both IL-4 and GM-CSF, suggesting that synergistic effects of both cytokines may in part provide the requisite STAT1 signaling intensity for DC maturation. Analyses of STAT1-/- DCs reveal a role for STAT1 in repressing CD86 expression in precursor DCs and up-regulating CD40, CD11c, and SOCS1 expression in mDCs. We further show that SOCS proteins are differentially induced by IL-4 and GM-CSF in DCs. SOCS1 is primarily induced by IL-4 through a STAT1-dependent mechanism, whereas SOCS3 is induced mainly by GM-CSF. Taken together, these results suggest that cytokine-induced maturation of DCs is under feedback regulation by SOCS proteins and that the switch from constitutive activation of the STAT6 pathway in iDCs to predominant use of STAT1 signals in mDC is mediated in part by STAT1-induced SOCS expression.
This article has been cited by other articles:
|
|
 |
|
  A. Larange, D. Antonios, M. Pallardy, and S. Kerdine-Romer TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation J. Leukoc. Biol., April 1, 2009; 85(4): 673 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shen, B. M. Tesar, W. E. Walker, and D. R. Goldstein Dual Signaling of MyD88 and TRIF Is Critical for Maximal TLR4-Induced Dendritic Cell Maturation J. Immunol., August 1, 2008; 181(3): 1849 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kim, S. H. Kim, S. Kim, D. Cho, and T. S. Kim AIMP1/p43 Protein Induces the Maturation of Bone Marrow-Derived Dendritic Cells with T Helper Type 1-Polarizing Ability J. Immunol., March 1, 2008; 180(5): 2894 - 2902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Sriram, C. Biswas, E. M. Behrens, J.-A. Dinnall, D. K. Shivers, M. Monestier, Y. Argon, and S. Gallucci IL-4 Suppresses Dendritic Cell Response to Type I Interferons J. Immunol., November 15, 2007; 179(10): 6446 - 6455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lehtonen, H. Ahlfors, V. Veckman, M. Miettinen, R. Lahesmaa, and I. Julkunen Gene expression profiling during differentiation of human monocytes to macrophages or dendritic cells J. Leukoc. Biol., September 1, 2007; 82(3): 710 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Johnson and P. Scott STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity to Leishmania major J. Immunol., June 1, 2007; 178(11): 7259 - 7266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Remoli, J. Ragimbeau, E. Giacomini, V. Gafa, M. Severa, R. Lande, S. Pellegrini, and E. M. Coccia NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation J. Leukoc. Biol., January 1, 2007; 81(1): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bartz, N. M. Avalos, A. Baetz, K. Heeg, and A. H. Dalpke Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation Blood, December 15, 2006; 108(13): 4102 - 4108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tortorella, O. Simone, G. Piazzolla, I. Stella, V. Cappiello, and S. Antonaci Role of Phosphoinositide 3-Kinase and Extracellular Signal-Regulated Kinase Pathways in Granulocyte Macrophage-Colony-Stimulating Factor Failure to Delay Fas-Induced Neutrophil Apoptosis in Elderly Humans J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2006; 61(11): 1111 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, N. Chu, A. Rostami, and G.-X. Zhang Dendritic Cells Transduced with SOCS-3 Exhibit a Tolerogenic/DC2 Phenotype That Directs Type 2 Th Cell Differentiation In Vitro and In Vivo J. Immunol., August 1, 2006; 177(3): 1679 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Strengell, A. Lehtonen, S. Matikainen, and I. Julkunen IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells J. Leukoc. Biol., June 1, 2006; 79(6): 1279 - 1285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Severa, M. E. Remoli, E. Giacomini, J. Ragimbeau, R. Lande, G. Uze, S. Pellegrini, and E. M. Coccia Differential responsiveness to IFN-{alpha} and IFN-{beta} of human mature DC through modulation of IFNAR expression J. Leukoc. Biol., June 1, 2006; 79(6): 1286 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tomic, D. White, Y. Shi, J. Mena, C. Hammond, L. He, R. L. Miller, and D. E. Spaner Sensitization of IL-2 Signaling through TLR-7 Enhances B Lymphoma Cell Immunogenicity J. Immunol., March 15, 2006; 176(6): 3830 - 3839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chiappelli The Molecular Immunology of Mucositis: Implications for Evidence-Based Research in Alternative and Complementary Palliative Treatments Evid. Based Complement. Altern. Med., December 1, 2005; 2(4): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Canfield, Y. Lee, A. Schroder, and P. Rothman Cutting Edge: IL-4 Induces Suppressor of Cytokine Signaling-3 Expression in B Cells by a Mechanism Dependent on Activation of p38 MAPK J. Immunol., March 1, 2005; 174(5): 2494 - 2498. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
