STAT4/6-dependent differential regulation of chemokine receptors.
The major cell fate decision of the CD4+ helper T cells is the development of Th1 and Th2 phenotype, the balance of which determines the outcome of a wide variety of autoimmune responses. Signal transducers and activators of transcription (STATs), in particular STAT4 and STAT6, are essential for the development of Th1 and Th2 cells, respectively. We used Balb/c mice lacking STAT4 or STAT6 to explore the ability of helper T cells to express chemokine receptors. We demonstrated that both STAT4-/- and STAT6-/- CD4+ lymphocytes showed impaired expansion as well as differentiation into IFN-gamma-secreting Th1 cells and IL2-, IL4-, IL10-secreting Th2 cells. Interestingly, the expression of chemokine receptors, which is STAT4/6-dependent, was differentially regulated via two distinct mechanisms, positively (CCR3, CCR4) and negatively (CCR5, CCR7). These results provide the basis for STAT-dependent differential regulation of chemokine receptors in Th subsets.
Kim
Soon Ha
SH
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Gunst
Kurt V
KV
Sarvetnick
N
N
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000502:physiology; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D019707:Receptors, Chemokine; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse