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

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

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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
Issue number23
StatePublished - Nov 10 1998


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