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J Immunol. 2016 Jun 15;196(12):4865-76. doi: 10.4049/jimmunol.1600066. Epub 2016 May 6.

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

Author information

1
Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
2
Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA 01199; and.
3
Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA 01199; and Department of Animal and Veterinary Sciences, University of Massachusetts at Amherst, Amherst, MA 01003.
4
Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119; Department of Animal and Veterinary Sciences, University of Massachusetts at Amherst, Amherst, MA 01003 clinton.mathias@wne.edu.

Abstract

IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/-) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcεRI expression on mast cells; and enhanced the production of mast cell cytokines. IL-10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms.

PMID:
27183617
PMCID:
PMC4893936
DOI:
10.4049/jimmunol.1600066
[Indexed for MEDLINE]
Free PMC Article

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