An enhanced immune response in mice lacking the transcription factor NFAT1

被引:317
作者
Xanthoudakis, S
Viola, JPB
Shaw, KTY
Luo, C
Wallace, JD
Bozza, PT
Curran, T
Rao, A
机构
[1] ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA
[2] HOFFMANN LA ROCHE INC, DEPT CNS RES, NEUROGENET PROGRAM, NUTLEY, NJ 07110 USA
[3] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA
[4] HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA
[5] HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, HARVARD THORNDIKE LAB, BOSTON, MA 02115 USA
[6] HARVARD UNIV, BETH ISRAEL HOSP,SCH MED,CHARLES A DANA RES INST, SCH MED, BOSTON, MA 02115 USA
关键词
D O I
10.1126/science.272.5263.892
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transcription factors of the NFAT family are thought to play a major role in regulating the expression of cytokine genes and other inducible genes during the immune response. The role of NFAT1 was investigated by targeted disruption of the NFAT1 gene. Unexpectedly, cells from NFAT1(-/-) mice showed increased primary responses to Leishmania major and mounted increased secondary responses to ovalbumin in vitro. In an in vivo model of allergic inflammation, the accumulation of eosinophils and levels of serum immunoglobulin E were increased in NFAT1(-/-) mice. These results suggest that NFAT1 exerts a negative regulatory influence on the immune response.
引用
收藏
页码:892 / 895
页数:4
相关论文
共 54 条
[1]   ACTIVATION AND EXPRESSION OF THE NUCLEAR FACTORS OF ACTIVATED T-CELLS, NFATP AND NFATC, IN HUMAN NATURAL-KILLER-CELLS - REGULATION UPON CD16 LIGAND-BINDING [J].
ARAMBURU, J ;
AZZONI, L ;
RAO, A ;
PERUSSIA, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) :801-810
[2]   ANTIVIRAL IMMUNE-RESPONSES IN MICE DEFICIENT FOR BOTH INTERLEUKIN-2 AND INTERLEUKIN-4 [J].
BACHMANN, MF ;
SCHORLE, H ;
KUHN, R ;
MULLER, W ;
HENGARTNER, H ;
ZINKERNAGEL, RM ;
HORAK, I .
JOURNAL OF VIROLOGY, 1995, 69 (08) :4842-4846
[3]   IL-5 ACCOUNTS FOR THE MOUSE PLEURAL EOSINOPHIL ACCUMULATION TRIGGERED BY ANTIGEN BUT NOT BY LPS [J].
BOZZA, PT ;
CASTROFARIANETO, HC ;
PENIDO, C ;
LARANGEIRA, AP ;
SILVA, PMR ;
MARTINS, MA ;
CORDEIRO, RSB .
IMMUNOPHARMACOLOGY, 1994, 27 (02) :131-136
[4]   THE IMMUNOSUPPRESSIVES FK-506 AND CYCLOSPORINE-A INHIBIT THE GENERATION OF PROTEIN FACTORS BINDING TO THE 2 PURINE BOXES OF THE INTERLEUKIN-2 ENHANCER [J].
BRABLETZ, T ;
PIETROWSKI, I ;
SERFLING, E .
NUCLEIC ACIDS RESEARCH, 1991, 19 (01) :61-67
[5]  
BRADLEY LM, 1995, J IMMUNOL, V155, P1713
[6]   IL-10 IMMUNOSUPPRESSION IN TRANSPLANTATION [J].
BROMBERG, JS .
CURRENT OPINION IN IMMUNOLOGY, 1995, 7 (05) :639-643
[7]   INDUCTION OF NF-AT IN NORMAL B-LYMPHOCYTES BY ANTIIMMUNOGLOBULIN OR CD40 LIGAND IN CONJUNCTION WITH IL4 [J].
CHOI, MSK ;
BRINES, RD ;
HOLMAN, MJ ;
KLAUS, GGB .
IMMUNITY, 1994, 1 (03) :179-187
[8]   MULTIPLE CLOSELY-LINKED NFAT-OCTAMER AND HMG I(Y) BINDING-SITES ARE PART OF THE INTERLEUKIN-4 PROMOTER [J].
CHUVPILO, S ;
SCHOMBERG, C ;
GERWIG, R ;
HEINFLING, A ;
REEVES, R ;
GRUMMT, F ;
SERFLING, E .
NUCLEIC ACIDS RESEARCH, 1993, 21 (24) :5694-5704
[9]   THE GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR INTERLEUKIN-3 LOCUS IS REGULATED BY AN INDUCIBLE CYCLOSPORINE A-SENSITIVE ENHANCER [J].
COCKERILL, PN ;
SHANNON, MF ;
BERT, AG ;
RYAN, GR ;
VADAS, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (06) :2466-2470
[10]  
COCKERILL PN, 1995, MOL CELL BIOL, V15, P2071