Abstract
T-bet is a transcription factor of the T-box family that regulates the expression of numerous immune system-associated genes. T-bet directs the acquisition of the Th1-associated genetic program in differentiating CD4(+) lymphocytes. It also influences the development of NK and NKT cells through its regulation of the IL-2/IL-15Rbeta-chain (CD122) and the trafficking of these lymphocytes through CxCR3. The temporal requirements of T-bet activity for the production of IFN-gamma and the regulation of CD122 and CxCR3 expression remain undefined. We produced an ectopically controllable form of T-bet by fusing its C-terminal domain with a mutated ligand-binding domain of human estrogen receptor alpha. By temporally controlling the expression of T-bet-estrogen receptor alpha by the addition or removal of 4-hydroxytamoxifen (4-HT), we show that IFN-gamma, CD122, and CxCR3 are direct gene targets of T-bet whose expression are acutely regulated by T-bet activity.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Differentiation / drug effects
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology*
-
Cell Movement / drug effects
-
Cell Movement / genetics
-
Cell Movement / immunology*
-
Estrogen Antagonists / pharmacology
-
Gene Expression Regulation / drug effects
-
Gene Expression Regulation / genetics
-
Gene Expression Regulation / immunology*
-
Interferon-gamma / biosynthesis
-
Interferon-gamma / immunology
-
Interleukin-2 Receptor beta Subunit / biosynthesis
-
Interleukin-2 Receptor beta Subunit / immunology
-
Killer Cells, Natural / immunology*
-
Killer Cells, Natural / metabolism
-
Mice
-
Mice, Knockout
-
Receptors, CXCR3
-
Receptors, Chemokine / biosynthesis
-
Receptors, Chemokine / immunology
-
Receptors, Estrogen / biosynthesis
-
Receptors, Estrogen / genetics
-
Receptors, Estrogen / immunology
-
T-Box Domain Proteins / deficiency
-
T-Box Domain Proteins / immunology*
-
T-Box Domain Proteins / metabolism
-
Tamoxifen / analogs & derivatives
-
Tamoxifen / pharmacology
-
Th1 Cells / immunology*
-
Th1 Cells / metabolism
Substances
-
CXCR3 protein, human
-
Cxcr3 protein, mouse
-
Estrogen Antagonists
-
Il2rb protein, mouse
-
Interleukin-2 Receptor beta Subunit
-
Receptors, CXCR3
-
Receptors, Chemokine
-
Receptors, Estrogen
-
T-Box Domain Proteins
-
T-box transcription factor TBX21
-
Tamoxifen
-
afimoxifene
-
Interferon-gamma