IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy
BackgroundThe 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 IgE-mediated MC activation, but also promotes IL-33-induced MC...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526498/full |
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| author | Dylan Krajewski Saurav Ranjitkar Nathan Jordan Sallie S. Schneider Clinton B. Mathias |
| author_facet | Dylan Krajewski Saurav Ranjitkar Nathan Jordan Sallie S. Schneider Clinton B. Mathias |
| author_sort | Dylan Krajewski |
| collection | DOAJ |
| description | BackgroundThe 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 IgE-mediated 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.MethodsTo 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.ResultsIL-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-10-depleted 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.ConclusionOur 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. |
| format | Article |
| id | doaj-art-e8f84142413245078a18be64c28568ad |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e8f84142413245078a18be64c28568ad2025-01-28T06:41:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15264981526498IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergyDylan Krajewski0Saurav Ranjitkar1Nathan Jordan2Sallie S. Schneider3Clinton B. Mathias4Department of Pharmaceutical and Administrative Sciences, Western New England University, Springfield, MA, United StatesDepartment of Nutritional Sciences, University of Connecticut, Storrs, CT, United StatesDepartment of Nutritional Sciences, University of Connecticut, Storrs, CT, United StatesPioneer Valley Life Sciences Institute, Baystate Medical Center, Springfield, MA, United StatesDepartment of Nutritional Sciences, University of Connecticut, Storrs, CT, United StatesBackgroundThe 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 IgE-mediated 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.MethodsTo 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.ResultsIL-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-10-depleted 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526498/fullmast cellsfood allergyIL-10IL-33allergy |
| spellingShingle | Dylan Krajewski Saurav Ranjitkar Nathan Jordan Sallie S. Schneider Clinton B. Mathias IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy Frontiers in Immunology mast cells food allergy IL-10 IL-33 allergy |
| title | IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy |
| title_full | IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy |
| title_fullStr | IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy |
| title_full_unstemmed | IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy |
| title_short | IL-33 signaling is dispensable for the IL-10-induced enhancement of mast cell responses during food allergy |
| title_sort | il 33 signaling is dispensable for the il 10 induced enhancement of mast cell responses during food allergy |
| topic | mast cells food allergy IL-10 IL-33 allergy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526498/full |
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