T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6

被引：122
作者：
Dent, AL
Hu-Li, J
Paul, WE
Staudt, LM
机构：
[1] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA
[2] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1998年 / 95卷 / 23期
关键词：
D O I：
10.1073/pnas.95.23.13823
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
An important signaling pathway for the differentiation of T helper type 2 (TH2) cells from uncommitted CD4 T cell precursors is activation of the STAT6 transcription factor by interleukin 4 (IL-4). The protooncogene BCL-6 is also involved in TH2 differentiation, as BCL-6 -/- mice develop an inflammation of the heart and lungs associated with an overproduction of TH2 cells. Surprisingly, IL-4 -/- BCL-6 -/- and STAT6 -/- BCL-6 -/- double-mutant mice developed the same TH2-type inflammation of the heart and lungs as is characteristic of BCL-6 -/- mice. Furthermore, a TH2 cytokine response developed in STAT6 -/- BCL-6 -/- and IL-4 -/- BCL-6 -/- mice after immunization with a conventional antigen in adjuvant. In contrast to these in vivo findings, STAT6 was required for the in vitro differentiation of BCL-6 -/- T cells into TH2 cells, BCL-6, a transcriptional repressor that can bind to the same DNA binding motifs as STAT transcription factors, seems to regulate TH2 responses in vivo by a pathway independent of IL-4 and STAT6.
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页码：13823 / 13828
页数：6
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