Publication Date:
2001-06-09
Description:
How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of TH1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-gamma synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mullen, A C -- High, F A -- Hutchins, A S -- Lee, H W -- Villarino, A V -- Livingston, D M -- Kung, A L -- Cereb, N -- Yao, T P -- Yang, S Y -- Reiner, S L -- AI-42370/AI/NIAID NIH HHS/ -- EY-07131/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 8;292(5523):1907-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11397944" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
CREB-Binding Protein
;
Cell Differentiation
;
Cell Division
;
Cell Lineage
;
Cells, Cultured
;
DNA-Binding Proteins/metabolism
;
Gene Expression Regulation
;
Histones/metabolism
;
Interferon-gamma/*biosynthesis/genetics
;
Interleukin-12/*metabolism
;
Lymphocyte Activation
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Nuclear Proteins/metabolism
;
RNA, Messenger/genetics/metabolism
;
Receptors, Interleukin/metabolism
;
Receptors, Interleukin-12
;
STAT4 Transcription Factor
;
Signal Transduction
;
T-Box Domain Proteins
;
Th1 Cells/cytology/*immunology/metabolism
;
Trans-Activators/metabolism
;
Transcription Factors/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
