STAT6-independent production of IL-4 by mast cells

The acquisition of an IL-4-producing phenotype in Th2 cells requires IL-4 s ignaling through the STAT6 pathway during T cell differentiation. In this s tudy we demonstrate that, unlike in naive T cells, IL-4 is not necessary fo r the development of an IL-4-producing phenotype in mast cells. Bone marrow -derived mast cell precursors from STAT6(-/-) mice can differentiate into m ature cells that express IL-4 levels comparable to those of wild-type mast cells. In differentiated mast cells, activation in the presence of neutrali zing anti-IL-4 antibodies or mutation of the consensus STAT6 sites does not diminish IL-4 promoter activity, indicating that IL-4 is not required for active transcription. Taken together, these data suggest that mast cell IL- 4 production is not STAT6 dependent, providing evidence that these cells co uld generate IL-4 needed for the initiation and amplification of an effecti ve Th2 immune response.