遗传vs环境：双胞胎研究揭示过敏免疫调控差异
2025/07/25
摘要
背景及目的：特应性疾病（如哮喘、过敏性鼻炎）的发病机制涉及遗传与环境的复杂交互作用，但其对免疫特征的具体影响尚不明确。本研究通过分析学龄双胞胎的免疫特征（包括细胞亚群和细胞因子反应），旨在量化遗传与环境因素的贡献，并探讨其与特应性的关联，为靶向治疗提供新思路。
研究方法：1.研究对象：93对6-12岁同卵（MZ）和异卵（DZ）双胞胎。2.免疫特征分析：流式细胞术量化B细胞、嗜碱性粒细胞、树突状细胞（DCs）等亚群。体外刺激实验：检测PBMC对刺激（如LPS、过敏原）的细胞因子反应（如Th1/Th2/调节性细胞因子）。双胞胎分析策略（比较MZ与DZ相关性）解析遗传度（heritability）。探究免疫特征与特应性（血清IgE升高或过敏症状）的关系。
主要结果：1.遗传主导的免疫特征：B细胞丰度遗传度最高（强遗传影响），嗜碱性粒细胞次之。IgE受体（FcεRI）表达：在嗜碱性粒细胞上受遗传显著调控，而在树突状细胞上主要受环境影响。2.环境主导的免疫特征：体外刺激后的细胞因子反应（如IL-4、IFN-γ）主要由环境因素塑造。3.特应性关联：特应性个体表现为B细胞和嗜碱性粒细胞增多，且嗜碱性粒细胞IgE受体表达升高。
结论与讨论：先天免疫细胞（如B细胞、嗜碱性粒细胞）的丰度及IgE受体表达具有高遗传性，提示遗传筛查对高风险个体的重要性。适应性免疫反应（如细胞因子分泌）更易受环境调控，支持通过早期环境干预（如微生物暴露）修正免疫失衡。本研究为针对环境敏感通路（如树突状细胞IgE受体）开发免疫调节策略提供新思路。
关键词：特应性、双胞胎研究、遗传度、B细胞、IgE受体、环境暴露
文献来源：Leffler J,et al.Atopy-related immune profiles are subject to genetic influence as evaluated using school-aged twin pairs.Sci Adv 2025 Jul 18;11(29):eads8033. doi: 10.1126/sciadv.ads8033
Abstract
The interaction of genetic and environmental contributions to immunological traits and their association with atopic disease remain unclear. Flow cytometry and in vitro cytokine responses were used to characterize immune profiles from 93 school-aged twin pairs. Using an established twin pair analytical strategy, the genetic and environmental influences on immunological traits were evaluated, along with their association with atopy. Our findings suggest strong genetic influence on several traits, particularly B cell abundance. In contrast, cytokine responses from in vitro stimulations appeared mainly shaped by environmental exposures. Regarding associations with atopy, greater abundance of both B cells and basophils were observed in atopic individuals as well as increased expression of the immunoglobulin E (IgE) receptor. Genetic influence appeared central to regulating IgE receptor expression on basophils, whereas expression on dendritic cells instead appeared sensitive to environmental exposures. Identifying environmentally regulated immune traits may facilitate the development of targeted therapies to limit the impact of atopic disease in the future.
背景及目的：特应性疾病（如哮喘、过敏性鼻炎）的发病机制涉及遗传与环境的复杂交互作用，但其对免疫特征的具体影响尚不明确。本研究通过分析学龄双胞胎的免疫特征（包括细胞亚群和细胞因子反应），旨在量化遗传与环境因素的贡献，并探讨其与特应性的关联，为靶向治疗提供新思路。
研究方法：1.研究对象：93对6-12岁同卵（MZ）和异卵（DZ）双胞胎。2.免疫特征分析：流式细胞术量化B细胞、嗜碱性粒细胞、树突状细胞（DCs）等亚群。体外刺激实验：检测PBMC对刺激（如LPS、过敏原）的细胞因子反应（如Th1/Th2/调节性细胞因子）。双胞胎分析策略（比较MZ与DZ相关性）解析遗传度（heritability）。探究免疫特征与特应性（血清IgE升高或过敏症状）的关系。
主要结果：1.遗传主导的免疫特征：B细胞丰度遗传度最高（强遗传影响），嗜碱性粒细胞次之。IgE受体（FcεRI）表达：在嗜碱性粒细胞上受遗传显著调控，而在树突状细胞上主要受环境影响。2.环境主导的免疫特征：体外刺激后的细胞因子反应（如IL-4、IFN-γ）主要由环境因素塑造。3.特应性关联：特应性个体表现为B细胞和嗜碱性粒细胞增多，且嗜碱性粒细胞IgE受体表达升高。
结论与讨论：先天免疫细胞（如B细胞、嗜碱性粒细胞）的丰度及IgE受体表达具有高遗传性，提示遗传筛查对高风险个体的重要性。适应性免疫反应（如细胞因子分泌）更易受环境调控，支持通过早期环境干预（如微生物暴露）修正免疫失衡。本研究为针对环境敏感通路（如树突状细胞IgE受体）开发免疫调节策略提供新思路。
关键词：特应性、双胞胎研究、遗传度、B细胞、IgE受体、环境暴露
文献来源：Leffler J,et al.Atopy-related immune profiles are subject to genetic influence as evaluated using school-aged twin pairs.Sci Adv 2025 Jul 18;11(29):eads8033. doi: 10.1126/sciadv.ads8033
（南方医科大学南方医院 欧阳文珊 赵海金）
Abstract
The interaction of genetic and environmental contributions to immunological traits and their association with atopic disease remain unclear. Flow cytometry and in vitro cytokine responses were used to characterize immune profiles from 93 school-aged twin pairs. Using an established twin pair analytical strategy, the genetic and environmental influences on immunological traits were evaluated, along with their association with atopy. Our findings suggest strong genetic influence on several traits, particularly B cell abundance. In contrast, cytokine responses from in vitro stimulations appeared mainly shaped by environmental exposures. Regarding associations with atopy, greater abundance of both B cells and basophils were observed in atopic individuals as well as increased expression of the immunoglobulin E (IgE) receptor. Genetic influence appeared central to regulating IgE receptor expression on basophils, whereas expression on dendritic cells instead appeared sensitive to environmental exposures. Identifying environmentally regulated immune traits may facilitate the development of targeted therapies to limit the impact of atopic disease in the future.
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