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

Alexander Dent, Jane Hu-Li, William E. Paul, Louis M. Staudt

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

An important signaling pathway for the differentiation oft 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.

Original languageEnglish (US)
Pages (from-to)13823-13828
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number23
DOIs
StatePublished - Nov 10 1998
Externally publishedYes

Fingerprint

STAT6 Transcription Factor
Interleukin-4
Pneumonia
STAT Transcription Factors
T-Lymphoid Precursor Cells
Nucleotide Motifs
Immunization
Cytokines
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. / Dent, Alexander; Hu-Li, Jane; Paul, William E.; Staudt, Louis M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 23, 10.11.1998, p. 13823-13828.

Research output: Contribution to journalArticle

@article{b4b3850aad3a44e7ac79cb6fc37d3cdb,
title = "T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6",
abstract = "An important signaling pathway for the differentiation oft 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.",
author = "Alexander Dent and Jane Hu-Li and Paul, {William E.} and Staudt, {Louis M.}",
year = "1998",
month = "11",
day = "10",
doi = "10.1073/pnas.95.23.13823",
language = "English (US)",
volume = "95",
pages = "13823--13828",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "23",

}

TY - JOUR

T1 - T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6

AU - Dent, Alexander

AU - Hu-Li, Jane

AU - Paul, William E.

AU - Staudt, Louis M.

PY - 1998/11/10

Y1 - 1998/11/10

N2 - An important signaling pathway for the differentiation oft 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.

AB - An important signaling pathway for the differentiation oft 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.

UR - http://www.scopus.com/inward/record.url?scp=0032506130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032506130&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.23.13823

DO - 10.1073/pnas.95.23.13823

M3 - Article

C2 - 9811885

AN - SCOPUS:0032506130

VL - 95

SP - 13823

EP - 13828

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -