IL-10 Neutralization Attenuates Mast Cell Responses in a Murine Model of Experimental Food Allergy.

Q3 Medicine ImmunoHorizons Pub Date : 2024-06-01 DOI:10.4049/immunohorizons.2400002
Dylan Krajewski, Saurav Ranjitkar, Caitlin Tedeschi, Nicole Maldonado Perez, Nathan Jordan, Mohamed Mire, Sallie S Schneider, Clinton B Mathias
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Abstract

IgE-mediated mast cell (MC) activation is a critical component of allergic responses to oral Ags. Several T cell-derived cytokines have been shown to promote MC reactivity, and we recently demonstrated a critical role for the cytokine IL-10 in mediating MC responses during food allergy. In this study, we further validate the role of IL-10 using Ab-mediated IL-10 depletion. IL-10 neutralization significantly attenuated MC responses, leading to decreased MC accumulation and activation, as well as inhibition of MC-mediated symptoms such as allergic diarrhea. This was accompanied by decreased Th2 cytokine gene expression, attenuated systemic T cell responses, and fewer CD4 T cells, B cells, and MCs in the spleen. Our data further confirm the role of IL-10 in driving MC responses and suggest that IL-10-responsive MCs may constitute an important player in allergic responses.

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IL-10 中和可减轻实验性食物过敏小鼠模型中的肥大细胞反应
IgE 介导的肥大细胞(MC)活化是口服抗原过敏反应的关键组成部分。已证明多种 T 细胞衍生的细胞因子可促进肥大细胞的反应性,我们最近证明了细胞因子 IL-10 在食物过敏期间介导 MC 反应的关键作用。在本研究中,我们利用抗体介导的 IL-10 去势进一步验证了 IL-10 的作用。IL-10中和可明显减弱MC反应,从而减少MC的聚集和激活,并抑制MC介导的过敏性腹泻等症状。与此同时,Th2 细胞因子基因表达减少,全身 T 细胞反应减弱,脾脏中的 CD4 T 细胞、B 细胞和 MC 减少。我们的数据进一步证实了IL-10在驱动MC反应中的作用,并表明IL-10反应性MC可能是过敏反应中的一个重要角色。
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