Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 335K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yao, Y. Articles by Chang, C.-H. Search for Related Content PubMed PubMed Citation Articles by Yao, Y. Articles by Chang, C.-H. Related Collections Related Article Social Bookmarking                      What's this?

¹ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202
² Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202

CORRESPONDENCE Cheong-Hee Chang: chechang{at}iupui.edu

Interleukin (IL)-4 is known to be the most potent cytokine that can initiate Th2 cell differentiation. Paradoxically, IL-4 instructs dendritic cells (DCs) to promote Th1 cell differentiation. We investigated the mechanisms by which IL-4 directs CD4 T cells toward the Th1 cell lineage. Our study demonstrates that the IL-4–mediated induction of Th1 cell differentiation requires IL-10 production by DCs. IL-4 treatment of DCs in the presence of lipopolysaccharide or CpG resulted in decreased production of IL-10, which was accompanied by enhanced IL-12 production. In IL-10–deficient DCs, the level of IL-12 was greatly elevated and, more importantly, the ability of IL-4 to up-regulate IL-12 was abrogated. Interestingly, IL-4 inhibited IL-10 production by DCs but not by B cells. The down-regulation of IL-10 gene expression by IL-4 depended on Stat6 and was at least partly caused by decreased histone acetylation of the IL-10 promoter. These data indicate that IL-4 plays a key role in inducing Th1 cell differentiation by instructing DCs to produce less IL-10.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Magalhaes, J. G., Fritz, J. H., Le Bourhis, L., Sellge, G., Travassos, L. H., Selvanantham, T., Girardin, S. E., Gommerman, J. L., Philpott, D. J. (2008). Nod2-Dependent Th2 Polarization of Antigen-Specific Immunity. J. Immunol. 181: 7925-7935 [Abstract] [Full Text]  
• Lam, Q. L. K., Zheng, B.-J., Jin, D.-Y., Cao, X., Lu, L. (2007). Leptin Induces CD40 Expression through the Activation of Akt in Murine Dendritic Cells. J. Biol. Chem. 282: 27587-27597 [Abstract] [Full Text]  
• Christy, A. L., Brown, M. A. (2007). The Multitasking Mast Cell: Positive and Negative Roles in the Progression of Autoimmunity. J. Immunol. 179: 2673-2679 [Abstract] [Full Text]  
• Nagase, H., Jones, K. M., Anderson, C. F., Noben-Trauth, N. (2007). Despite Increased CD4+Foxp3+ Cells within the Infection Site, BALB/c IL-4 Receptor-Deficient Mice Reveal CD4+Foxp3-Negative T Cells as a Source of IL-10 in Leishmania major Susceptibility. J. Immunol. 179: 2435-2444 [Abstract] [Full Text]  
• Nigg, A. P., Zahn, S., Ruckerl, D., Holscher, C., Yoshimoto, T., Ehrchen, J. M., Wolbing, F., Udey, M. C., von Stebut, E. (2007). Dendritic Cell-Derived IL-12p40 Homodimer Contributes to Susceptibility in Cutaneous Leishmaniasis in BALB/c Mice. J. Immunol. 178: 7251-7258 [Abstract] [Full Text]  
• Staples, K. J., Smallie, T., Williams, L. M., Foey, A., Burke, B., Foxwell, B. M. J., Ziegler-Heitbrock, L. (2007). IL-10 Induces IL-10 in Primary Human Monocyte-Derived Macrophages via the Transcription Factor Stat3. J. Immunol. 178: 4779-4785 [Abstract] [Full Text]  
• Flores, R. R., Diggs, K. A., Tait, L. M., Morel, P. A. (2007). IFN-{gamma} Negatively Regulates CpG-Induced IL-10 in Bone Marrow-Derived Dendritic Cells. J. Immunol. 178: 211-218 [Abstract] [Full Text]  
• Schmidt, N. W., Thieu, V. T., Mann, B. A., Ahyi, A.-N. N., Kaplan, M. H. (2006). Bruton's Tyrosine Kinase Is Required for TLR-Induced IL-10 Production. J. Immunol. 177: 7203-7210 [Abstract] [Full Text]  
• Lu, T., Newton, C., Perkins, I., Friedman, H., Klein, T. W. (2006). Cannabinoid Treatment Suppresses the T-Helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated with Legionella pneumophila Infection. J. Pharmacol. Exp. Ther. 319: 269-276 [Abstract] [Full Text]  
• Marcais, A., Coupet, C.-A., Walzer, T., Tomkowiak, M., Ghittoni, R., Marvel, J. (2006). Cell-Autonomous CCL5 Transcription by Memory CD8 T Cells Is Regulated by IL-4. J. Immunol. 177: 4451-4457 [Abstract] [Full Text]  
• Kean, D. E., Goodridge, H. S., McGuinness, S., Harnett, M. M., Alcocer, M. J. C., Harnett, W. (2006). Differential Polarization of Immune Responses by Plant 2S Seed Albumins, Ber e 1, and SFA8. J. Immunol. 177: 1561-1566 [Abstract] [Full Text]  
• Yao, Y., Xu, Q., Kwon, M.-J., Matta, R., Liu, Y., Hong, S.-C., Chang, C.-H. (2006). ERK and p38 MAPK Signaling Pathways Negatively Regulate CIITA Gene Expression in Dendritic Cells and Macrophages. J. Immunol. 177: 70-76 [Abstract] [Full Text]  
• Zhao, Q., Wang, X., Nelin, L. D., Yao, Y., Matta, R., Manson, M. E., Baliga, R. S., Meng, X., Smith, C. V., Bauer, J. A., Chang, C.-H., Liu, Y. (2006). MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock. JEM 203: 131-140 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS