IL-4 inhibits mouse mast cell Fc epsilonRI expression through a STAT6-dependent mechanism.
Mast cell activation by IgE-mediated stimuli is a central event in atopic disease. The regulation of the mast cell high affinity receptor, Fc epsilonRI, is poorly understood. We show that IL-4 can inhibit Fc epsilonRI expression on mouse bone marrow-derived mast cells and fetal liver-derived mast cell progenitors. This effect could be observed at 2.5 ng/ml IL-4 and was dose dependent. IL-4-mediated inhibition of cultured BMMC required 4 days of stimulation and was sustained at maximum levels for at least 21 days. The inhibition of Fc epsilonRI expression resulted in decreased sensitivity to IgE-mediated stimulation, as measured by serotonin release, and the induction of mRNA for IL-4, IL-5, IL-6, and IL-13. Additionally, IL-4 could abrogate the IgE-mediated increase in Fc epsilonRI expression. Lastly, IL-4-mediated inhibition was dependent upon expression of the STAT6 transcription factor, as STAT6-deficient bone marrow-derived mast cells did not decrease Fc epsilonRI levels in response to IL-4. These data argue for a homeostatic role of IL-4 in the regulation of Fc epsilonRI expression, a role that could be critical to understanding atopic disease.
Ryan
J J
JJ
Department of Biology, Virginia Commonwealth University, Richmond 23284, USA. jjryan@saturn.vcu.edu
DeSimone
S
S
Klisch
G
G
Shelburne
C
C
McReynolds
L J
LJ
Han
K
K
Kovacs
R
R
Mirmonsef
P
P
Huff
T F
TF
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000196:embryology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics; D050800:STAT6 Transcription Factor; D012701:Serotonin / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*
D007378:Interleukins; D012333:RNA, Messenger; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D012701:Serotonin