title: IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.
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.
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Polukort
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rovatti
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
authors.forename: Logan
authors.initials: L
authors.lastname: Carlson
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
authors.forename: Chelsea
authors.initials: C
authors.lastname: Thompson
authors.affiliation: Pioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA 01199; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ser-Dolansky
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119;
authors.forename: Shannon R M
authors.initials: SR
authors.lastname: Kinney
authors.affiliation: 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.
authors.forename: Sallie S
authors.identifier: 0000-0003-0093-4308
authors.initials: SS
authors.lastname: Schneider
authors.affiliation: 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.
authors.forename: Clinton B
authors.identifier: 0000-0002-0223-4842
authors.initials: CB
authors.lastname: Mathias
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003967:Diarrhea; D005512:Food Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D016753:Interleukin-10 / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology*; D007422:Intestines / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; D017455:Receptors, IgE; D016753:Interleukin-10; D007073:Immunoglobulin E; D010047:Ovalbumin