KLF2 Transcription-Factor Deficiency in T Cells Results in Unrestrained Cytokine Production and Upregulation of Bystander Chemokine Receptors

被引：180

作者：

Weinreich, Michael A. ^{[1
]}

Takada, Kensuke ^{[1
]}

Skon, Cara ^{[1
]}

Reiner, Steven L. ^{[2
,3
]}

Jameson, Stephen C. ^{[1
]}

Hogquist, Kristin A. ^{[1
]}

机构：

[1] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[2] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

来源：

IMMUNITY | 2009年 / 31卷 / 01期

关键词：

LYMPHOCYTE EGRESS; EXPRESSION; BET; TRAFFICKING; MIGRATION; LACKING; S1P(1); LKLF;

D O I：

10.1016/j.immuni.2009.05.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 up-regulation 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.

引用

页码：122 / 130

页数：9