The role of STAT6 in mast cell IL-4 production.
Interleukin (IL)-4 has an important role in regulating antibody production and inflammation. The major IL-4 producers are CD4+ T cells, but the development of an IL-4-producing phenotype in these cells requires IL-4 signaling through the STAT6 pathway during differentiation. The cellular source of this early IL-4 is not known, but mast cells are a possible candidate due to their immediate and indiscriminate release of IL-4 upon activation. In this review we summarize the evidence that STAT6 signaling is not required for mast cell IL-4 production, which is consistent with their possible role as a link between the innate immune response and T-cell activation. We also describe an isoform of STAT6 that is expressed in mast cells and that appears to act as a repressor of IL-4 transcription. This STAT6 signaling pathway may be part of a feedback mechanism to protect surrounding tissues from IL-4-mediated inflammation during an infection.
Sherman
M A
MA
Department of Pathology, Emory University, Atlanta, GA,  USA. msherma@emory.edu
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D007239:Infections / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000378:metabolism*; D008415:Mastocytosis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D005810:Multigene Family; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D016207:Cytokines; D020033:Protein Isoforms; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4