波士顿儿童医院Raif S. Geha团队的研究显示,金黄色葡萄球菌暴露期间皮肤抗原致敏引起嗜碱性粒细胞和白细胞介素-4依赖性夸大的食物过敏反应。2025年9月25日出版的《免疫学》发表了这项成果。
研究小组发现伴有金黄色葡萄球菌皮肤定植和食物过敏的AD患者血清IL-4浓度升高。通过AD小鼠模型,该课题组证明了表皮抗原与产生超抗原的金黄色葡萄球菌或葡萄球菌肠毒素B(SEB)一起应用,引起了全身抗原特异性T-2(Th2)反应的增强和血清IL-4浓度的升高。T细胞来源的IL-4作用于肠上皮细胞,增强肠通透性和肠内抗原刺激的过敏反应。CD40依赖性SEB与角质形成细胞结合触发IL-33释放,引导T细胞产生IL-3,引发皮肤引流淋巴结(dLNs)的嗜碱性粒细胞内流。嗜碱性粒细胞衍生的IL-4通过皮肤dLNs中携带抗原的树突状细胞增强Th2细胞极化。这些结果表明,治疗性干预可能会减轻AD患者的食物过敏。
研究人员表示,金黄色葡萄球菌皮肤定植与特应性皮炎(AD)患者食物过敏的关联机制尚不清楚。白细胞介素-4 (IL-4)在食物过敏中起重要作用。
附:英文原文
Title: S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis
Author: Mrinmoy Das, Mohammed Alasharee, Brian Woods, Saikat Mukherjee, Shira Kim, Megan Elkins, Jacqueline Ngo, Logan Magin, Maheshwor Timilshina, Juan Manuel Leyva-Castillo, Kenneth M. Murphy, Robert M. Anthony, Ana Flávia Santarine Laureano, George F. Murphy, Shannon McNamee, Frank Brombacher, Simon P. Hogan, Jerrold R. Turner, Shabnam Abtahi, Wanda Phipatanakul, Donald Y.M. Leung, Elena Goleva, Hans C. Oettgen, Mei Li, Janet Chou, Patrick M. Schlievert, Fred D. Finkelman, Raif S. Geha
Issue&Volume: 2025-09-25
Abstract: The mechanism of the association of S. aureus skin colonization with food allergy in atopic dermatitis (AD) is unknown. Interleukin-4 (IL-4) plays an important role in food allergy. We found elevated serum IL-4 concentrations in AD patients with S. aureus skin colonization and food allergy. Using an AD mouse model, we demonstrated that epicutaneous application of antigen together with superantigen-producing S. aureus, or staphylococcal enterotoxin B (SEB), caused a heightened systemic antigen-specific T helper-2 (Th2) response and elevated serum IL-4 concentrations. T cell-derived IL-4 acted on intestinal epithelial cells to enhance intestinal permeability and anaphylaxis to enteral antigen challenge. CD40-dependent SEB binding to keratinocytes triggered IL-33 release, which caused T cells to produce IL-3 that elicited a basophil influx in skin-draining lymph nodes (dLNs). Basophil-derived IL-4 augmented Th2 cell polarization by antigen-bearing dendritic cells from skin dLNs. These results suggest therapeutic interventions that might attenuate food allergy in AD patients.
DOI: 10.1016/j.immuni.2025.09.001
Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00412-1
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:43.474
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