|
|
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.
 Previous Article | Next Article 
Submitted March 11, 2005
Accepted August 4, 2005
A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells
Gregory H Underhill, Dimitrios G Zisoulis, K P Kolli, Lesley G Ellies, Jamey D Marth, and Geoffrey S Kansas*
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University Medical School, Chicago, IL, USA
Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute and University of California San Diego, La Jolla, CA, USA
* Corresponding author; email: gsk{at}northwestern.edu.
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 to WT Th1 cells. Enforced expression of T-bet in WT Th0 cells only modestly upregulated 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 C2GlcNAcT-I, but no differences in levels of ST3Gal-IV. Further, we show that T-bet is responsible for the Stat4-independent increase in Th1 cells of FucT-VII. We also identify ST3Gal-VI, which is thought to play an important role in E- and P-selectin ligand formation, as an 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:
|
|
|
|
 
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]
|
|
|
| |
