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Science 10 May 1996:
Vol. 272. no. 5263, pp. 892 - 895
DOI: 10.1126/science.272.5263.892
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Reports

An Enhanced Immune Response in Mice Lacking the Transcription Factor NFAT1

Steven Xanthoudakis, Joao P. B. Viola, Karen T. Y. Shaw, Chun Luo, James D. Wallace, * Patricia T. Bozza, Tom Curran, dagger Anjana Rao dagger

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.

S. Xanthoudakis and J. D. Wallace, Neurogenetics Program, Department of CNS Research, Hoffmann-La Roche, Nutley, NJ 07110, USA.
J. P. B. Viola, K. T. Y. Shaw, C. Luo, A. Rao, Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
P. T. Bozza, Harvard Thorndike Laboratory and Charles A. Dana Research Institute, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA 02115, USA.
T. Curran, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
* Present address: Lexicon Genetics, 4000 Research Forest Drive, The Woodlands, TX 77381, USA.
dagger To whom correspondence should be addressed.


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L. J. Sun, B. R. Peterson, and G. L. Verdine (1997)
PNAS 94, 4919-4924
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A critical arginine residue mediates cooperativity in the contact interface between transcription factors NFAT and AP-1.
B. R. Peterson, L. J. Sun, and G. L. Verdine (1996)
PNAS 93, 13671-13676
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Glycogen Synthase Kinase-3 Inhibits the DNA Binding Activity of NFATc.
J. W. Neal and N. A. Clipstone (2001)
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Silencer Activity of NFATc2 in the Interleukin-12 Receptor beta 2 Proximal Promoter in Human T Helper Cells.
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Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression.
J. Rengarajan, K. A. Mowen, K. D. McBride, E. D. Smith, H. Singh, and L. H. Glimcher (2002)
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