IL-10 suppresses mast cell IgE receptor expression and signaling in vitro and in vivo.
Mast cells are known for their roles in allergy, asthma, systemic anaphylaxis, and inflammatory disease. IL-10 can regulate inflammatory responses and may serve as a natural regulator of mast cell function. We examined the effects of IL-10 on in vitro-cultured mouse and human mast cells, and evaluated the effects of IL-10 on FcepsilonRI in vivo using mouse models. IgE receptor signaling events were also assessed in the presence or absence of IL-10. IL-10 inhibited mouse mast cell FcepsilonRI expression in vitro through a Stat3-dependent process. This down-regulation was consistent in mice tested in vivo, and also on cultured human mast cells. IL-10 diminished expression of the signaling molecules Syk, Fyn, Akt, and Stat5, which could explain its ability to inhibit IgE-mediated activation. Studies of passive systemic anaphylaxis in IL-10-transgenic mice showed that IL-10 overexpression reduced the IgE-mediated anaphylactic response. These data suggest an important regulatory role for IL-10 in dampening mast cell FcepsilonRI expression and function. IL-10 may hence serve as a mediator of mast cell homeostasis, preventing excessive activation and the development of chronic inflammation.
Kennedy Norton
Sarah
S
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA.
Barnstein
Brian
B
Brenzovich
Jennifer
J
Bailey
Daniel P
DP
Kashyap
Mohit
M
Speiran
Kelly
K
Ford
Jill
J
Conrad
Daniel
D
Watowich
Stephanie
S
Moralle
Matthew R
MR
Kepley
Christopher L
CL
Murray
Peter J
PJ
Ryan
John J
JJ
D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage / Q000502:physiology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D046509:Tissue Culture Techniques
D017455:Receptors, IgE; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10