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.