T-bet is required for optimal proinflammatory CD4+ T-cell trafficking.
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.
Lord
Graham M
GM
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Rao
Ravi M
RM
Choe
Hyeryun
H
Sullivan
Brandon M
BM
Lichtman
Andrew H
AH
Luscinskas
F William
FW
Glimcher
Laurie H
LH
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019707:Receptors, Chemokine; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors