Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy

Abstract

SUMMARY Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin (IL)-9. However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9 and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.

Human Vδ2 T cells are a major source of interleukin-9

“…The best characterized is the Th9 subset of CD4 T cells, but IL-9 production has also been found in CD8 T cells (29), innate lymphoid cells (30), and mast cells (31). So far, there is only one report of IL-9 production by γδ T cells in Schistosoma japonicum-infected mice (32).…”

Immunity to gastrointestinal nematode infections

“…As with the role of IL-5 in promoting eosinophil responses, IL-9 acts mainly as a maturation factor for mucosal mast cells, [90][91][92] and is largely T cell derived, [93][94][95] although it can be secreted by ILC2, 96 as well as by mast cells themselves 97,98 that in turn promote enhanced secretion of IL-25, IL-33, and TSLP from epithelial cells. 99 As a result, T. muris and H. polygyrus expulsion are impaired in mast cell-deficient mice 99,100 as well as upon administration of neutralizing IL-9 antibodies, 101,102 although it should be noted that studies using mast celldeficient mice (c-kit mutants) suffer from possible confounding factors given the role for c-kit on many other cell types, and thus remain to be clarified.…”

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

“…Therefore, targeting IL-33/ST2 might be considered therapeutically to attenuate ongoing hepatic inflammation and fibrosis in human patients. 13,14 MATERIALS AND METHODS Patients A total of 24 patients who underwent partial hepatectomy due to early-stage hepatocellular carcinoma with liver cirrhosis at The First Affiliated Hospital of Nanjing Medical University from January 2012 to December 2013 were involved in the study. Normal liver tissues were obtained as controls from 20 Chinese patients with benign disease, such as hemangioma.…”