SEARCH:   Advanced

Blood, 1 December 2005, Vol. 106, No. 12, pp. 3867-3873. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-0984. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-0984v1 106/12/3867    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Underhill, G. H. Articles by Kansas, G. S. Search for Related Content PubMed PubMed Citation Articles by Underhill, G. H. Articles by Kansas, G. S. Related Collections Immunobiology Cell Adhesion and Motility Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells Greg H. Underhill, Dimitrios G. Zisoulis, K. Pallav Kolli, Lesley G. Ellies, Jamey D. Marth, and Geoffrey S. Kansas From the Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL; and the Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA. Proinflammatory T helper 1 (Th1) cells express high levels of carbohydrate ligands for the endothelial selectins, but the molecular basis for this phenotype is incompletely understood. We document here a significant role in selectin ligand formation for the recently described Th1 transcription factor T-bet. Th1 cells generated from T-bet-/- mice showed significantly lower levels of ligands for both E-selectin and P-selectin, compared with wild-type (WT) Th1 cells. Enforced expression of T-bet in WT Th0 cells only modestly up-regulated P-selectin ligands and had no effect on E-selectin ligands. To define a mechanism for the defects observed in T-bet-/- mice, we examined expression of glycosyltransferases involved in selectin ligand biosynthesis. T-bet-/- Th1 cells expressed significantly lower levels of core 2 1,6 N-acetylglucosaminyltransferase I (C2GlcNAcT-I), but no differences in levels of 2,3-sialyltransferase IV (ST3Gal-IV). Further, we show that T-bet is responsible for the signal transducer and activator of transcription 4 (Stat4)–independent increase in Th1 cells of fucosyltransferase VII (FucT-VII). We also identify ST3Gal-VI, which is thought to play an important role in E- and P-selectin ligand formation, as an interleukin 12 (IL-12)–regulated, T-bet–dependent gene. These data show that T-bet controls selectin ligand formation in Th1 cells via control of expression of multiple key enzymes in response to IL-12 signaling and establishes an independent transcriptional pathway for control of Th1 cell traffic. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T cells bet on sugars to help Linda G. Baum Blood 2005 106: 3677-3678. [Full Text] [PDF] This article has been cited by other articles: C. Mo, W. Chearwae, J. T. O'Malley, S. M. Adams, S. Kanakasabai, C. C. Walline, G. L. Stritesky, S. R. Good, N. B. Perumal, M. H. Kaplan, et al. Stat4 Isoforms Differentially Regulate Inflammation and Demyelination in Experimental Allergic Encephalomyelitis J. Immunol., October 15, 2008; 181(8): 5681 - 5690. [Abstract] [Full Text] [PDF] H. Jin, Y. Kang, L. Zhao, C. Xiao, Y. Hu, R. She, Y. Yu, X. Du, G. Zhao, T. Ng, et al. Induction of Adaptive T Regulatory Cells That Suppress the Allergic Response by Coimmunization of DNA and Protein Vaccines J. Immunol., April 15, 2008; 180(8): 5360 - 5372. [Abstract] [Full Text] [PDF] M. E. Gainers, L. Descheny, S. R. Barthel, L. Liu, M.-A. Wurbel, and C. J. Dimitroff Skin-Homing Receptors on Effector Leukocytes Are Differentially Sensitive to Glyco-Metabolic Antagonism in Allergic Contact Dermatitis J. Immunol., December 15, 2007; 179(12): 8509 - 8518. [Abstract] [Full Text] [PDF] S. Jennrich, B. A. Ratsch, A. Hamann, and U. Syrbe Long-Term Commitment to Inflammation-Seeking Homing in CD4+ Effector Cells J. Immunol., June 15, 2007; 178(12): 8073 - 8080. [Abstract] [Full Text] [PDF] G. Tellides and J. S. Pober Interferon-{gamma} Axis in Graft Arteriosclerosis Circ. Res., March 16, 2007; 100(5): 622 - 632. [Abstract] [Full Text] [PDF] U. Syrbe, U. Hoffmann, K. Schlawe, O. Liesenfeld, K. Erb, and A. Hamann Microenvironment-Dependent Requirement of STAT4 for the Induction of P-Selectin Ligands and Effector Cytokines on CD4+ T Cells in Healthy and Parasite-Infected Mice J. Immunol., December 1, 2006; 177(11): 7673 - 7679. [Abstract] [Full Text] [PDF] M. Nasirikenari, B. H. Segal, J. R. Ostberg, A. Urbasic, and J. T. Lau Altered granulopoietic profile and exaggerated acute neutrophilic inflammation in mice with targeted deficiency in the sialyltransferase ST6Gal I Blood, November 15, 2006; 108(10): 3397 - 3405. [Abstract] [Full Text] [PDF] G.-Y. Chen, H. Osada, L. F. Santamaria-Babi, and R. Kannagi Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes PNAS, November 7, 2006; 103(45): 16894 - 16899. [Abstract] [Full Text] [PDF] V. R. Taqueti, N. Grabie, R. Colvin, H. Pang, P. Jarolim, A. D. Luster, L. H. Glimcher, and A. H. Lichtman T-bet Controls Pathogenicity of CTLs in the Heart by Separable Effects on Migration and Effector Activity J. Immunol., November 1, 2006; 177(9): 5890 - 5901. [Abstract] [Full Text] [PDF] P. V. Cabrera, M. Amano, J. Mitoma, J. Chan, J. Said, M. Fukuda, and L. G. Baum Haploinsufficiency of C2GnT-I glycosyltransferase renders T lymphoma cells resistant to cell death Blood, October 1, 2006; 108(7): 2399 - 2406. [Abstract] [Full Text] [PDF] A. N. Mathur, H.-C. Chang, D. G. Zisoulis, R. Kapur, M. L. Belladonna, G. S. Kansas, and M. H. Kaplan T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype Blood, September 1, 2006; 108(5): 1595 - 1601. [Abstract] [Full Text] [PDF] E. M. Comelli, M. Sutton-Smith, Q. Yan, M. Amado, M. Panico, T. Gilmartin, T. Whisenant, C. M. Lanigan, S. R. Head, D. Goldberg, et al. Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling of N-Linked Glycans J. Immunol., August 15, 2006; 177(4): 2431 - 2440. [Abstract] [Full Text] [PDF] T. Usui, J. C. Preiss, Y. Kanno, Z. J. Yao, J. H. Bream, J. J. O'Shea, and W. Strober T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription J. Exp. Med., March 20, 2006; 203(3): 755 - 766. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020