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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 |
doi: 10.3389/fimmu.2025.1526498
IL-33 Signaling is Dispensable for the IL-10-induced Enhancement of Mast Cell Responses During Food Allergy
Provisionally accepted- 1 Western New England University, Springfield, Massachusetts, United States
- 2 University of Connecticut, Storrs, United States
- 3 Baystate Medical Center, Springfield, Massachusetts, United States
The IL-33/ST2 axis plays a pivotal role in the development of IgE-mediated mast cell (MC) responses during food allergy. We recently demonstrated that the pleiotropic cytokine, IL-10, not only exerts proinflammatory effects on IgEmediated MC activation, but also promotes IL-33-induced MC responses. However, whether IL-33 is necessary for IL-10's proinflammatory effects has not been examined. To therefore determine the role of the IL-33/ST2 axis in this pathway, we assessed the effects of IL-10 on IgE-mediated MC activation and food allergy development in wild-type (WT) and ST2 -/-mice. IL-10 stimulation significantly enhanced IL-33 gene expression, ST2 receptor expression, cytokine production, mMCP-1 secretion, and proliferation in IgE and antigen-activated bone marrow-derived MCs (BMMCs) from WT mice. ST2 -/-BMMCs exhibited reduced cytokine secretion in response to IgE-dependent activation. However, IL-10 enhanced cytokine production, mMCP-1 secretion, and proliferation in these cells as well. To further assess the role of IL-10, food allergy was induced in WT and ST2 -/-mice subjected to antibody-mediated IL-10 depletion. IL-10depleted WT mice exhibited a significant attenuation in MC-mediated responses to OVA challenge. While ST2 -/-mice also exhibited a profound suppression of MC responses, IL-10 depletion had no additional effects. However, ST2 -/-/IL-10 -/- mice exhibited further decreases in OVA-IgE and antigen-specific MC activation compared to ST2 -/-mice. Our data demonstrates that IL-10 can enhance MC responses in both WT and ST2 -/-mice, further corroborating its proinflammatory effects on MCs and suggesting that they are not regulated by IL-33 signaling.
Keywords: MCS, food allergy, IL-10, IL-33, allergy
Received: 11 Nov 2024; Accepted: 08 Jan 2025.
Copyright: © 2025 Krajewski, Ranjitkar, Schneider and Mathias. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Clinton Mathias, University of Connecticut, Storrs, United States
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