Kim Yu Rin, Jung YunJae, Kang Insug, Yeo Eui-Ju
Department of Biomedical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2025 Jul 23;26(15):7101. doi: 10.3390/ijms26157101.
Autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors-including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs-as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors-including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms-further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases.
系统性红斑狼疮和干燥综合征等自身免疫性疾病在患病率、严重程度和临床结局方面存在明显的性别差异，女性受影响的比例过高。新出现的证据表明，免疫和炎症反应中的性别差异是造成这种偏差的关键因素。遗传因素，包括性染色体、X染色体失活偏倚和性别偏向的微小RNA，以及性激素和怀孕，以性别特异性方式调节基因表达和免疫细胞功能。此外，性激素依赖性表观遗传修饰影响关键免疫调节因子的转录。这些遗传和激素因素共同塑造了多种免疫细胞类型的激活、分化和效应功能。环境因素，包括感染、肠道微生物群、环境化学物质和污染物，以及饮食、吸烟、紫外线暴露、酒精和咖啡因摄入、体育活动和昼夜节律等生活方式行为，进一步以性别依赖的方式调节免疫功能和自身免疫性疾病的发病机制。这些机制共同导致了女性自身免疫风险的增加和独特的临床特征。对性别偏向的免疫调节有更深入的了解将有助于识别新的生物标志物，实现患者分层，并为自身免疫性疾病的性别特异性诊断和治疗策略的开发提供信息。
