| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 Chain Expression and Signaling
* Mucosal Immunity and
Clinical Immunology Sections, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, and
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
In this study we demonstrated that CD4+ T cells from
STAT4-/- mice exhibit reduced IL-12R expression and poor
IL-12R signaling function. This raised the question of whether
activated STAT4 participates in Th1 cell development mainly through its
effects on IL-12 signaling. In a first approach to this question we
determined the capacity of CD4+ T cells from
STAT4-/- bearing an IL-12R
2 chain transgene (and thus
capable of normal IL-12R expression and signaling) to undergo Th1
differentiation when stimulated by Con A and APCs. We found that such
cells were still unable to exhibit IL-12-mediated IFN-
production.
In a second approach to this question, we created Th2 cell lines (D10
cells) transfected with STAT4-expressing plasmids with various
tyrosine
phenylalanine mutations and CD4+ T cell lines
from IL-122-/- mice infected with retroviruses
expressing similarly STAT4 mutations that nevertheless express surface
IL-12R2 chains. We then showed that constructs that were unable to
support STAT4 tyrosine phosphorylation (in D10 cells) as a result of
mutation were also incapable of supporting IL-12-induced IFN-
production (in IL-12R2-/- cells). Thus, by two
complementary approaches we demonstrated that activated STAT4 has an
essential downstream role in Th1 cell differentiation that is
independent of its role in the support of IL-12R2 chain signaling.
This implies that STAT4 is an essential element in the early events of
Th1 differentiation.
This article has been cited by other articles:
|
|
 |
|
  C. KIYOHARA, M. WASHIO, T. HORIUCHI, Y. TADA, T. ASAMI, S. IDE, T. ATSUMI, G. KOBASHI, and H. TAKAHASHI Cigarette Smoking, STAT4 and TNFRSF1B Polymorphisms, and Systemic Lupus Erythematosus in a Japanese Population J Rheumatol, October 1, 2009; 36(10): 2195 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Jang, Y. M. Son, G. R. Kim, Y. J. Lee, W. K. Lee, S. H. Cha, S. H. Han, and C.-H. Yun Synergistic production of interleukin-23 by dendritic cells derived from cord blood in response to costimulation with LPS and IL-12 J. Leukoc. Biol., September 1, 2009; 86(3): 691 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Platten, S. Youssef, E. M. Hur, P. P. Ho, M. H. Han, T. V. Lanz, L. K. Phillips, M. J. Goldstein, R. Bhat, C. S. Raine, et al. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity PNAS, September 1, 2009; 106(35): 14948 - 14953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Chang, L. Han, R. Goswami, E. T. Nguyen, D. Pelloso, M. J. Robertson, and M. H. Kaplan Impaired development of human Th1 cells in patients with deficient expression of STAT4 Blood, June 4, 2009; 113(23): 5887 - 5890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Van, W.-H. Lee, S. Ortiz, M.-H. Lee, H.-J. Qin, and C.-P. Liu All-trans Retinoic Acid Inhibits Type 1 Diabetes by T Regulatory (Treg)-Dependent Suppression of Interferon-{gamma}-Producing T-cells Without Affecting Th17 Cells Diabetes, January 1, 2009; 58(1): 146 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yang, J. Xu, Y. Niu, J. S. Bromberg, and Y. Ding T-bet and Eomesodermin Play Critical Roles in Directing T Cell Differentiation to Th1 versus Th17 J. Immunol., December 15, 2008; 181(12): 8700 - 8710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rhodes and T. J. Vyse The genetics of SLE: an update in the light of genome-wide association studies Rheumatology, November 1, 2008; 47(11): 1603 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. O'Malley, R. D. Eri, G. L. Stritesky, A. N. Mathur, H.-C. Chang, H. HogenEsch, M. Srinivasan, and M. H. Kaplan STAT4 Isoforms Differentially Regulate Th1 Cytokine Production and the Severity of Inflammatory Bowel Disease J. Immunol., October 1, 2008; 181(7): 5062 - 5070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Ruby, R. Montler, R. Zheng, S. Shu, and A. D. Weinberg IL-12 Is Required for Anti-OX40-Mediated CD4 T Cell Survival J. Immunol., February 15, 2008; 180(4): 2140 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. F. Remmers, R. M. Plenge, A. T. Lee, R. R. Graham, G. Hom, T. W. Behrens, P. I.W. de Bakker, J. M. Le, H.-S. Lee, F. Batliwalla, et al. STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus N. Engl. J. Med., September 6, 2007; 357(10): 977 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pellicano, L. Sebkova, G. Monteleone, G. Guarnieri, M. Imeneo, F. Pallone, and F. Luzza Interleukin-12 Drives the Th1 Signaling Pathway in Helicobacter pylori-Infected Human Gastric Mucosa Infect. Immun., April 1, 2007; 75(4): 1738 - 1744. [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. Nebozhyn, A. Loboda, L. Kari, A. H. Rook, E. C. Vonderheid, S. Lessin, C. Berger, R. Edelson, C. Nichols, M. Yousef, et al. Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy Blood, April 15, 2006; 107(8): 3189 - 3196. [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]
|
|
|
|
 |
|
 E M Coccia, M E Remoli, C Di Giacinto, B Del Zotto, E Giacomini, G Monteleone, and M Boirivant Cholera toxin subunit B inhibits IL-12 and IFN-{gamma} production and signaling in experimental colitis and Crohn's disease Gut, November 1, 2005; 54(11): 1558 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Corn, C. Hunter, H.-C. Liou, U. Siebenlist, and M. R. Boothby Opposing Roles for RelB and Bcl-3 in Regulation of T-Box Expressed in T Cells, GATA-3, and Th Effector Differentiation J. Immunol., August 15, 2005; 175(4): 2102 - 2110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sanchez-Guajardo, J. A. M. Borghans, M.-E. Marquez, S. Garcia, and A. A. Freitas Different Competitive Capacities of Stat4- and Stat6-Deficient CD4+ T Cells during Lymphophenia-Driven Proliferation J. Immunol., February 1, 2005; 174(3): 1178 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Toyoda, M. Ido, T. Hayashi, E. C. Gabazza, K. Suzuki, J. Bu, S. Tanaka, T. Nakano, H. Kamiya, J. Chipeta, et al. Impairment of IL-12-Dependent STAT4 Nuclear Translocation in a Patient with Recurrent Mycobacterium avium Infection J. Immunol., March 15, 2004; 172(6): 3905 - 3912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O'Sullivan, H.-C. Chang, Q. Yu, and M. H. Kaplan STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus J. Biol. Chem., February 20, 2004; 279(8): 7339 - 7345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Chang, S. Zhang, I. Oldham, L. Naeger, T. Hoey, and M. H. Kaplan STAT4 Requires the N-terminal Domain for Efficient Phosphorylation J. Biol. Chem., August 22, 2003; 278(34): 32471 - 32477. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
