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KLF2 transcription-factor deficiency in T cells results in unrestrained cytokine production and upregulation of bystander chemokine receptors.

The transcription factor KLF2 regulates T cell trafficking by promoting expression of the lipid-binding receptor S1P(1) and the selectin CD62L. Recently, it was proposed that KLF2 also represses the expression of chemokine receptors. We confirmed the upregulation of the chemokine receptor CXCR3 on KLF2-deficient T cells. However, we showed that this was a cell-nonautonomous effect, as revealed by CXCR3 upregulation on wild-type bystander cells in mixed bone-marrow chimeras with KLF2-deficient cells. Furthermore, KLF2-deficient T cells overproduced IL-4, leading to the upregulation of CXCR3 through an IL-4-receptor- and eomesodermin-dependent pathway. Consistent with the increased IL-4 production, we found high concentrations of serum IgE in mice with T cell-specific KLF2 deficiency. Our findings support a model where KLF2 regulates T cell trafficking by direct regulation of S1P(1) and CD62L and restrains spontaneous cytokine production in naive T cells.

Pubmed ID: 19592277

Authors

  • Weinreich MA
  • Takada K
  • Skon C
  • Reiner SL
  • Jameson SC
  • Hogquist KA

Journal

Immunity

Publication Data

July 17, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI038903
  • Agency: NIAID NIH HHS, Id: R01 AI038903-10
  • Agency: NIAID NIH HHS, Id: R01 AI039560
  • Agency: NIAID NIH HHS, Id: R01 AI039560-06
  • Agency: NIAID NIH HHS, Id: R01 AI042370
  • Agency: NIAID NIH HHS, Id: R01 AI042370-12
  • Agency: NIAID NIH HHS, Id: R01 AI076458
  • Agency: NIAID NIH HHS, Id: R01 AI076458-02
  • Agency: NIAID NIH HHS, Id: R01-AI38903
  • Agency: NIAID NIH HHS, Id: R01-AI39560
  • Agency: NIAID NIH HHS, Id: R37 AI038903
  • Agency: NIAID NIH HHS, Id: T32 AI007313
  • Agency: NIAID NIH HHS, Id: T32 AI007313-21
  • Agency: NIAID NIH HHS, Id: T32-AI007313

Mesh Terms

  • Animals
  • Immunoglobulin E
  • Interleukin-4
  • Kruppel-Like Transcription Factors
  • L-Selectin
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CXCR3
  • Receptors, Lysosphingolipid
  • T-Box Domain Proteins
  • T-Lymphocytes
  • Up-Regulation