Original Article

Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (CIITA) Expression

Correspondence to: Walter Reith, Department of Genetics and Microbiology, University of Geneva Medical School, CMU, 1 rue Michel-Servet, 1211 Geneva, Switzerland. Tel:41-22-702-56-66 Fax:41-22-702-57-02 E-mail:walter.reith{at}medecine.unige.ch.

Cell surface expression of major histocompatibility complex class II (MHCII) molecules is increased during the maturation of dendritic cells (DCs). This enhances their ability to present antigen and activate naive CD4⁺ T cells. In contrast to increased cell surface MHCII expression, de novo biosynthesis of MHCII mRNA is turned off during DC maturation. We show here that this is due to a remarkably rapid reduction in the synthesis of class II transactivator (CIITA) mRNA and protein. This reduction in CIITA expression occurs in human monocyte-derived DCs and mouse bone marrow–derived DCs, and is triggered by a variety of different maturation stimuli, including lipopolysaccharide, tumor necrosis factor , CD40 ligand, interferon , and infection with Salmonella typhimurium or Sendai virus. It is also observed in vivo in splenic DCs in acute myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalitis. The arrest in CIITA expression is the result of a transcriptional inactivation of the MHC2TA gene. This is mediated by a global repression mechanism implicating histone deacetylation over a large domain spanning the entire MHC2TA regulatory region.

Key Words: MHC class II, class II transactivator, experimental autoimmune encephalitis, bare lymphocyte syndrome, histone deacetylation

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

This article has been cited by other articles:

• Chang, Y.-C., Chen, T.-C., Lee, C.-T., Yang, C.-Y., Wang, H.-W., Wang, C.-C., Hsieh, S.-L. (2008). Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3. Blood 111: 5054-5063 [Abstract] [Full Text]  
• Steiner, Q.-G., Otten, L. A., Hicks, M. J., Kaya, G., Grosjean, F., Saeuberli, E., Lavanchy, C., Beermann, F., McClain, K. L., Acha-Orbea, H. (2008). In vivo transformation of mouse conventional CD8{alpha}+ dendritic cells leads to progressive multisystem histiocytosis. Blood 111: 2073-2082 [Abstract] [Full Text]  
• Grassi, F., Tell, G., Robbie-Ryan, M., Gao, Y., Terauchi, M., Yang, X., Romanello, M., Jones, D. P., Weitzmann, M. N., Pacifici, R. (2007). Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. Proc. Natl. Acad. Sci. USA 104: 15087-15092 [Abstract] [Full Text]  
• Herrmann, T. L., Agrawal, R. S., Connolly, S. F., McCaffrey, R. L., Schlomann, J., Kusner, D. J. (2007). MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II. J. Leukoc. Biol. 82: 686-699 [Abstract] [Full Text]  
• Casals, C., Barrachina, M., Serra, M., Lloberas, J., Celada, A. (2007). Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA. J. Immunol. 178: 6307-6315 [Abstract] [Full Text]  
• Rybtsova, N., Leimgruber, E., Seguin-Estevez, Q., Dunand-Sauthier, I., Krawczyk, M., Reith, W. (2007). Transcription-coupled deposition of histone modifications during MHC class II gene activation. Nucleic Acids Res 35: 3431-3441 [Abstract] [Full Text]  
• Krawczyk, M., Leimgruber, E., Seguin-Estevez, Q., Dunand-Sauthier, I., Barras, E., Reith, W. (2007). Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes. Nucleic Acids Res 35: 595-605 [Abstract] [Full Text]  
• Green, M. R., Yoon, H., Boss, J. M. (2006). Epigenetic Regulation during B Cell Differentiation Controls CIITA Promoter Accessibility. J. Immunol. 177: 3865-3873 [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]  
• Pennini, M. E., Pai, R. K., Schultz, D. C., Boom, W. H., Harding, C. V. (2006). Mycobacterium tuberculosis 19-kDa Lipoprotein Inhibits IFN-{gamma}-Induced Chromatin Remodeling of MHC2TA by TLR2 and MAPK Signaling. J. Immunol. 176: 4323-4330 [Abstract] [Full Text]  
• Chou, S.-D., Khan, A. N. H., Magner, W. J., Tomasi, T. B. (2005). Histone acetylation regulates the cell type specific CIITA promoters, MHC class II expression and antigen presentation in tumor cells. Int Immunol 17: 1483-1494 [Abstract] [Full Text]  
• Wang, A. H., Gregoire, S., Zika, E., Xiao, L., Li, C. S., Li, H., Wright, K. L., Ting, J. P., Yang, X.-J. (2005). Identification of the Ankyrin Repeat Proteins ANKRA and RFXANK as Novel Partners of Class IIa Histone Deacetylases. J. Biol. Chem. 280: 29117-29127 [Abstract] [Full Text]  
• Bellemare-Pelletier, A., Tremblay, J., Beaulieu, S., Boulassel, M.-R., Routy, J.-P., Massie, B., Lapointe, R., Thibodeau, J. (2005). HLA-DO transduced in human monocyte-derived dendritic cells modulates MHC class II antigen processing. J. Leukoc. Biol. 78: 95-105 [Abstract] [Full Text]  
• Yee, C. S. K., Yao, Y., Xu, Q., McCarthy, B., Sun-Lin, D., Tone, M., Waldmann, H., Chang, C.-H. (2005). Enhanced Production of IL-10 by Dendritic Cells Deficient in CIITA. J. Immunol. 174: 1222-1229 [Abstract] [Full Text]  
• van der Stoep, N., Quinten, E., Rezende, M. M., van den Elsen, P. J. (2004). E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivator promoter III (CIITA-PIII). Blood 104: 2849-2857 [Abstract] [Full Text]  
• Hafsi, N., Voland, P., Schwendy, S., Rad, R., Reindl, W., Gerhard, M., Prinz, C. (2004). Human Dendritic Cells Respond to Helicobacter pylori, Promoting NK Cell and Th1-Effector Responses In Vitro. J. Immunol. 173: 1249-1257 [Abstract] [Full Text]  
• Nolan, K. F., Strong, V., Soler, D., Fairchild, P. J., Cobbold, S. P., Croxton, R., Gonzalo, J.-A., Rubio, A., Wells, M., Waldmann, H. (2004). IL-10-Conditioned Dendritic Cells, Decommissioned for Recruitment of Adaptive Immunity, Elicit Innate Inflammatory Gene Products in Response to Danger Signals. J. Immunol. 172: 2201-2209 [Abstract] [Full Text]  
• Takeuchi, O., Sims, T. N., Takei, Y., Ramassar, V., Famulski, K. S., Halloran, P. F. (2003). Differential Usage of Class II Transactivator Promoters PI and PIV during Inflammation and Injury in Kidney. J. Am. Soc. Nephrol. 14: 2823-2832 [Abstract] [Full Text]  
• Kuchtey, J., Pennini, M., Pai, R. K., Harding, C. V. (2003). CpG DNA Induces a Class II Transactivator-Independent Increase in Class II MHC by Stabilizing Class II MHC mRNA in B Lymphocytes. J. Immunol. 171: 2320-2325 [Abstract] [Full Text]  
• Hornell, T. M. C., Beresford, G. W., Bushey, A., Boss, J. M., Mellins, E. D. (2003). Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor. J. Immunol. 171: 2374-2383 [Abstract] [Full Text]  
• Pai, R. K., Convery, M., Hamilton, T. A., Boom, W. H., Harding, C. V. (2003). Inhibition of IFN-{gamma}-Induced Class II Transactivator Expression by a 19-kDa Lipoprotein from Mycobacterium tuberculosis: A Potential Mechanism for Immune Evasion. J. Immunol. 171: 175-184 [Abstract] [Full Text]  
• Kanaseki, T., Ikeda, H., Takamura, Y., Toyota, M., Hirohashi, Y., Tokino, T., Himi, T., Sato, N. (2003). Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas. J. Immunol. 170: 4980-4985 [Abstract] [Full Text]  
• Zika, E., Greer, S. F., Zhu, X.-S., Ting, J. P.-Y. (2003). Histone Deacetylase 1/mSin3A Disrupts Gamma Interferon-Induced CIITA Function and Major Histocompatibility Complex Class II Enhanceosome Formation. Mol. Cell. Biol. 23: 3091-3102 [Abstract] [Full Text]  
• Waldburger, J.-M., Rossi, S., Hollander, G. A., Rodewald, H.-R., Reith, W., Acha-Orbea, H. (2003). Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells. Blood 101: 3550-3559 [Abstract] [Full Text]  
• Otten, L. A., Tacchini-Cottier, F., Lohoff, M., Annunziato, F., Cosmi, L., Scarpellino, L., Louis, J., Steimle, V., Reith, W., Acha-Orbea, H. (2003). Deregulated MHC Class II Transactivator Expression Leads to a Strong Th2 Bias in CD4+ T Lymphocytes. J. Immunol. 170: 1150-1157 [Abstract] [Full Text]  
• Tsujimura, H., Tamura, T., Gongora, C., Aliberti, J., Reis e Sousa, C., Sher, A., Ozato, K. (2003). ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro. Blood 101: 961-969 [Abstract] [Full Text]  
• Fumeaux, T., Pugin, J. (2002). Role of Interleukin-10 in the Intracellular Sequestration of Human Leukocyte Antigen-DR in Monocytes during Septic Shock. Am. J. Respir. Crit. Care Med. 166: 1475-1482 [Abstract] [Full Text]  
• Shtrichman, R., Heithoff, D. M., Mahan, M. J., Samuel, C. E. (2002). Tissue Selectivity of Interferon-Stimulated Gene Expression in Mice Infected with Dam+ versus Dam-Salmonella enterica Serovar Typhimurium Strains. Infect. Immun. 70: 5579-5588 [Abstract] [Full Text]  
• Wong, A. W., Ghosh, N., McKinnon, K. P., Reed, W., Piskurich, J. F., Wright, K. L., Ting, J. P.-Y. (2002). Regulation and Specificity of MHC2TA Promoter Usage in Human Primary T Lymphocytes and Cell Line. J. Immunol. 169: 3112-3119 [Abstract] [Full Text]  
• Barbieri, G., Deffrennes, V., Prod'homme, T., Vedrenne, J., Baton, F., Cortes, C., Fischer, A., Bono, M.-R., Lisowska-Grospierre, B., Charron, D., Alcaide-Loridan, C. (2002). Isoforms of the class II transactivator protein. Int Immunol 14: 839-848 [Abstract] [Full Text]  
• Pai, R. K., Askew, D., Boom, W. H., Harding, C. V. (2002). Regulation of Class II MHC Expression in APCs: Roles of Types I, III, and IV Class II Transactivator. J. Immunol. 169: 1326-1333 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS