Duhamel Marie, Salzet Michel
Univ. Lille, Inserm, Centre Hospitalier Universitaire (CHU) Lille, U1192 - Protéomique Réponse Inflammatoire Spectrométrie de Masse (PRISM), Lille, France.
Institut Universitaire de France, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, 1 rue Descartes, Paris, France.
Front Immunol. 2025 May 8;16:1595764. doi: 10.3389/fimmu.2025.1595764. eCollection 2025.
Immunologists generally view the notion of self and non-self as part of a broader, more contextual understanding of immune function, rather than a rigid dogma. While the classical paradigm that the primary role of the immune system is to recognize and eliminate anything foreign once provided a unifying basis for explaining tolerance and rejection, numerous discoveries have focused attention on how immune responses are finely tuned by a range of contextual cues, including tissue signals, hygienist theory, molecular mimicry, symbiotic microbes, metabolic factors and epigenetic modifications. Maternal-fetal tolerance and the persistence of microchimeric cells in adults demonstrate that genetically foreign cells can be actively integrated into the host, challenging the simple assumption that 'foreign' equals unconditional attack. Similarly, research into the microbiome, the virome and the phenomenon of trained innate immunity has shown that there can be beneficial or even essential relationships between the body and what has traditionally been labelled 'non-self'. Over the last decade, the idea that the immune system strictly enforces a binary distinction has instead evolved towards a model in which it continuously interprets signals of damage or perturbation, manages complex ecological relationships with commensal or latent organisms, and recalibrates according to the organism's life stage and environment. There remains a recognition that clonal deletion and negative selection in the thymus, together with MHC-bound peptide recognition, still underlie many core processes, and in certain clinical contexts, such as acute transplant rejection or the prevention of autoimmunity, an approximate self-non-self-categorization is directly relevant. Overall, however, the field recognizes that 'self' is not a static attribute defined once and for all, but rather a dynamic and context-dependent state that continues to be shaped by microbial symbioses, epigenetic reprogramming and immunoregulatory networks throughout an individual's lifespan.
免疫学家通常将自我与非自我的概念视为对免疫功能更广泛、更具情境性的理解的一部分，而非严格的教条。虽然经典范式认为免疫系统的主要作用是识别并清除任何外来物质，这曾为解释耐受性和排斥反应提供了统一基础，但众多发现已将注意力集中在免疫反应如何通过一系列情境线索进行精细调节上，这些线索包括组织信号、卫生学理论、分子模拟、共生微生物、代谢因素和表观遗传修饰。母胎耐受性以及成人体内微嵌合细胞的持续存在表明，基因上的外来细胞可以被积极整合到宿主中，这挑战了“外来”等同于无条件攻击的简单假设。同样，对微生物组、病毒组以及训练有素的先天免疫现象的研究表明，身体与传统上被标记为“非自我”的物质之间可能存在有益甚至是必不可少的关系。在过去十年中，免疫系统严格执行二元区分的观念已逐渐演变为一种模型，即免疫系统不断解读损伤或扰动信号，管理与共生或潜伏生物的复杂生态关系，并根据生物体的生命阶段和环境进行重新校准。人们仍然认识到，胸腺中的克隆清除和阴性选择，以及与主要组织相容性复合体（MHC）结合的肽识别，仍然是许多核心过程的基础，并且在某些临床情况下，如急性移植排斥或自身免疫的预防中，大致的自我 - 非自我分类直接相关。然而，总体而言，该领域认识到“自我”不是一个一劳永逸定义的静态属性，而是一种动态的、依赖情境的状态，在个体的一生中，它会持续受到微生物共生、表观遗传重编程和免疫调节网络的塑造。
