Abstract
Inflammatory responses are controlled by T helper 1 (Th1) lymphocytes. An important function of this polarity is the ability of T cells to traffick appropriately in vivo. This differential trafficking is dependent upon the binding of P-selectin glycoprotein ligand-1 to P- and E-selectin on inflamed endothelium as well as the expression of specific chemokine receptors. Here we show that in the absence of T-box expressed in T cells (T-bet), selective migration of T cells in vivo is completely abrogated and that T-bet regulates the binding of CD4(+) T cells to P-selectin. T-bet is also required for the expression of the chemokine receptor CXCR3. Thus, T-bet controls Th1-cell migration to inflammatory sites, which has fundamental consequences for the control of immunologic disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Movement / genetics
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Cell Movement / immunology*
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Cells, Cultured
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E-Selectin / immunology
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E-Selectin / metabolism
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Inflammation / genetics
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Inflammation / immunology
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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P-Selectin / immunology
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P-Selectin / metabolism
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Protein Binding / immunology
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Receptors, Chemokine / genetics
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Receptors, Chemokine / immunology
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T-Box Domain Proteins
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Th1 Cells / immunology*
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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E-Selectin
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Membrane Glycoproteins
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P-Selectin
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P-selectin ligand protein
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Receptors, Chemokine
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transcription Factors