美国耶鲁大学医学院R. Medzhitov团队的最新研究揭示了环境驱动的免疫印记可以防止过敏。该项研究成果发表在2026年1月28日出版的《自然》上。

在这里，该课题组研究人员展示了过敏性疾病的主题模型，暴露于免疫刺激环境中产生交叉反应性适应性免疫记忆，在过敏原暴露时，这种记忆与受阻的II型免疫反应相跟踪。该课题组人员发现交叉反应性适应性免疫的参与可以防止未来的过敏致敏，并抑制已建立的过敏反应。在耐受性背景下的交叉反应性也可以防止过敏，即使在低蛋白质序列相似性的情况下，其效果也可以扩展到抗原性复杂的暴露。他们的发现证明了环境和过敏之间的机制关系，对自然环境下的适应性免疫功能具有普遍意义。

据了解，过敏性疾病是由过度旺盛的II型免疫反应引起的，这些反应是针对环境抗原的。过敏状态的典型特征是过敏原反应性免疫球蛋白E （IgE）的存在，在遇到过敏原时触发肥大细胞脱颗粒，表现为瘙痒、水肿，严重时还会出现过敏反应。在过去的一个世纪里，过敏性疾病的患病率显著增加，这表明是环境因素而不是遗传因素介导了这种变化。虽然存在许多将环境与过敏联系起来的假设，但支持环境介导的过敏保护的生物学机制尚不清楚。

附：英文原文

Title: Environmentally driven immune imprinting protects against allergy

Author: Erickson, S., Lauring, B., Cullen, J., Medzhitov, R.

Issue&Volume: 2026-01-28

Abstract: Allergic diseases are caused by overexuberant type II immune responses mounted against environmental antigens1. The allergic state is typified by the presence of allergen-reactive immunoglobulin E (IgE), which triggers mast cell degranulation upon allergen encounter, manifesting in pruritis, oedema and, in severe cases, anaphylaxis. Over the past century, the prevalence of allergic diseases has increased markedly, suggesting that environmental rather than genetic factors are mediating this change2. Although many hypotheses connecting environment to allergy exist3,4,5,6, the biological mechanisms that underpin environmentally mediated protection from allergy are unknown. Here we show, using a mouse model of allergic disease, that exposure to immunostimulatory environments generated cross-reactive adaptive immune memory, which tracked with obstructed type II immune responses upon allergen exposure. We found that engagement of cross-reactive adaptive immunity protected against future allergic sensitization and suppressed established allergic responses. Cross-reactivity in a tolerogenic context also prevented allergy, with the effect extending across antigenically complex exposures even at low protein sequence similarity. Our findings demonstrate a mechanistic relationship between environment and allergy, with general implications for adaptive immune function in natural settings.

DOI: 10.1038/s41586-025-10001-5

Source: https://www.nature.com/articles/s41586-025-10001-5