Divergent Effects of Acute and Prolonged Interleukin 33 Exposure on Mast Cell IgE-Mediated Functions

Front Immunol. 2019 Jun 19;10:1361. doi: 10.3389/fimmu.2019.01361. eCollection 2019.


Background: Epithelial cytokines, including IL-33 and Thymic stromal lymphopoietin (TSLP), have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells. In the current study, we investigated how acute vs. prolonged exposure of mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation. Methods: Human lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP. Results: IL-33 induced the release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, 4 days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in FcεRI expression. Conclusion: We show that IL-33 plays dual roles in mast cells, in which its acute effects include cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel regulatory pathway that modulates IgE-mediated human mast cell responses.

Keywords: FcεRI; IL-33; IgE; TSLP; mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Degranulation / immunology
  • Cytokines / metabolism
  • Humans
  • Immunoglobulin E / immunology*
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Interleukin-33 / metabolism*
  • Mast Cells / immunology*
  • Mast Cells / metabolism*
  • Prostaglandins D / metabolism
  • Receptors, IgE / metabolism
  • Thymic Stromal Lymphopoietin


  • Biomarkers
  • Cytokines
  • IL33 protein, human
  • Inflammation Mediators
  • Interleukin-33
  • Prostaglandins D
  • Receptors, IgE
  • Immunoglobulin E
  • Thymic Stromal Lymphopoietin