STAT4/6-dependent differential regulation of chemokine receptors

Soon Ha Kim, Kurt V. Gunst, N. Sarvetnick

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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-γ-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.

Original languageEnglish (US)
Pages (from-to)250-257
Number of pages8
JournalClinical Immunology
Volume118
Issue number2-3
DOIs
StatePublished - Feb 2006

Keywords

  • Cell expansion
  • Chemokine receptors
  • Signal transducers and activators of transcription (STAT)4/STAT6
  • Th1/ Th2 phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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