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

• Published in: Frontiers in immunology Vol. 10; p. 1361
• Main Authors: Rönnberg, Elin, Ghaib, Avan, Ceriol, Carlos, Enoksson, Mattias, Arock, Michel, Säfholm, Jesper, Ekoff, Maria, Nilsson, Gunnar
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2019
• Subjects: Fc epsilon RI; FcεRI; IgE; IL-33; Immunology; mast cells; Medicin och hälsovetenskap; TSLP; FcεRI; TSLP; mast cells; IL-33; IgE
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01361

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. 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. 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. 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.