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 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.
authors.affiliation: Metabolism Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Dent
authors.forename: J
authors.initials: J
authors.lastname: Hu-Li
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
authors.forename: L M
authors.initials: LM
authors.lastname: Staudt
mesh_terms: D000818:Animals; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D015847:Interleukin-4 / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*
chemical_list: D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4