A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells

被引：56

作者：

Vacchio, Melanie S. ^{[1
]}

Wang, Lie ^{[1
]}

Bouladoux, Nicolas ^{[2
]}

Carpenter, Andrea C. ^{[1
]}

Xiong, Yumei ^{[1
]}

Wohlfert, Elizabeth ^{[1
,2
,4
]}

Song, Ki-Duk ^{[3
,5
]}

Belkaid, Yasmine ^{[2
]}

Love, Paul E. ^{[3
]}

Bosselut, Remy ^{[1
]}

机构：

[1] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Dev Biol, Program Genom Differentiat, NIH, Bethesda, MD USA

[4] SUNY Buffalo, Sch Med & Biomed Sci, Dept Microbiol & Immunol, Buffalo, NY 14260 USA

[5] Seoul Natl Univ, Ctr Agr Biomat, Seoul, South Korea

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 10期

基金：

美国国家卫生研究院;

关键词：

ZINC-FINGER PROTEIN; CD4-CD8 LINEAGE DIFFERENTIATION; HELPER TYPE-1 CELLS; EXPRESSION; REPRESSION; COMMITMENT; THYMOCYTES; LIGAND; RUNX3; GENE;

D O I：

10.1038/ni.2960

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 ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses and was required for proper differentiation of types 1 and 2 helper T cells in vivo by restraining the expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell differentiation. The transcription factor LRF acts redundantly with ThPOK to prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses.

引用

页码：947 / U192

页数：11

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