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IL-10 Suppresses Mast Cell IgE Receptor Expression and Signaling In Vitro and In Vivo

2008; American Association of Immunologists; Volume: 180; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.180.5.2848

1550-6606

Sarah K. Norton, Brian Barnstein, Jennifer Brenzovich, Daniel P. Bailey, Mohit Kashyap, Kelly Speiran, Jill Ford, Daniel H. Conrad, Stephanie S. Watowich, Matthew R. Moralle, Christopher L. Kepley, Peter J. Murray, John Ryan,

Asthma and respiratory diseases

Abstract 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 FcεRI 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 FcεRI 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 FcεRI expression and function. IL-10 may hence serve as a mediator of mast cell homeostasis, preventing excessive activation and the development of chronic inflammation.