Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1.
Transcription factors of the NFAT family play a critical role in the immune response by activating the expression of cytokines and other inducible genes in antigen-stimulated cells. Here we show that a member of this family, NFAT1, is involved in down-regulating the late phase of IL-4 gene transcription, thus inhibiting T helper 2 responses. Whereas stimulated T cells from wild-type mice show a transient increase and then a rapid decline in the steady-state levels of IL-4 mRNA in vitro, the levels of IL-4 gene transcripts in NFAT1-deficient T cells are maintained at high levels under the same conditions. Consistent with this observation, NFAT1-/- mice are more susceptible to infection with Leishmania major. This report provides evidence that NFAT proteins regulate not only the initiation but also the termination of gene transcription.
Kiani
A
A
The Center For Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Viola
J P
JP
Lichtman
A H
AH
Rao
A
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D015847:Interleukin-4 / Q000235:genetics*; D018320:Leishmania major / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D015847:Interleukin-4