STAT6-independent production of IL-4 by mast cells.
The acquisition of an IL-4-producing phenotype in Th2 cells requires IL-4 signaling through the STAT6 pathway during T cell differentiation. In this study we demonstrate that, unlike in naive T cells, IL-4 is not necessary for the development of an IL-4-producing phenotype in mast cells. Bone marrow-derived mast cell precursors from STAT6-/- mice can differentiate into mature cells that express IL-4 levels comparable to those of wild-type mast cells. In differentiated mast cells, activation in the presence of neutralizing 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 could generate IL-4 needed for the initiation and amplification of an effective Th2 immune response.
Sherman
M A
MA
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Secor
V H
VH
Lee
S K
SK
Lopez
R D
RD
Brown
M A
MA
D000818:Animals; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*
D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4