Moreno R J, Abu Amara R, Ashwood P
Department of Medical Microbiology and Immunology, UC Davis, CA, USA; The M.I.N.D. Institute, University of California at Davis, CA, USA.
Department of Medical Microbiology and Immunology, UC Davis, CA, USA; The M.I.N.D. Institute, University of California at Davis, CA, USA.
Brain Behav Immun. 2025 Jan;123:1147-1158. doi: 10.1016/j.bbi.2024.10.009. Epub 2024 Oct 6.
Autism spectrum disorder (ASD) is a highly heterogeneous disorder characterized by impairments in social, communicative, and restrictive behaviors. Over the past 20 years, research has highlighted the role of the immune system in regulating neurodevelopment and behavior. In ASD, immune abnormalities are frequently observed, such as elevations in pro-inflammatory cytokines, alterations in immune cell frequencies, and dysregulated mechanisms of immune suppression. The adaptive immune system - the branch of the immune system conferring cellular immunity - may be involved in the etiology of ASD. Specifically, dysregulated T cell activity, characterized by altered cellular function and increased cytokine release, presence of inflammatory phenotypes and altered cellular signaling, has been consistently observed in several studies across multiple laboratories and geographic regions. Similarly, mechanisms regulating their activation are also disrupted. T cells at homeostasis coordinate the healthy development of the central nervous system (CNS) during early prenatal and postnatal development, and aid in CNS maintenance into adulthood. Thus, T cell dysregulation may play a role in neurodevelopment and the behavioral and cognitive manifestations observed in ASD. Outside of the CNS, aberrant T cell activity may also be responsible for the increased frequency of immune based conditions in the ASD population, such as allergies, gut inflammation and autoimmunity. In this review, we will discuss the current understanding of T cell biology in ASD and speculate on mechanisms behind their dysregulation. This review also evaluates how aberrant T cell biology affects gastrointestinal issues and behavior in the context of ASD.
自闭症谱系障碍（ASD）是一种高度异质性疾病，其特征为社交、沟通及限制性行为受损。在过去20年里，研究突出了免疫系统在调节神经发育和行为方面的作用。在ASD中，经常观察到免疫异常，如促炎细胞因子升高、免疫细胞频率改变以及免疫抑制机制失调。适应性免疫系统——赋予细胞免疫的免疫系统分支——可能参与了ASD的病因。具体而言，在多个实验室和不同地理区域开展的多项研究中，始终观察到以细胞功能改变、细胞因子释放增加、炎症表型存在以及细胞信号传导改变为特征的T细胞活性失调。同样，调节其激活的机制也受到破坏。处于稳态的T细胞在产前和产后早期发育阶段协调中枢神经系统（CNS）的健康发育，并在成年期帮助维持CNS功能。因此，T细胞失调可能在神经发育以及ASD中观察到的行为和认知表现中发挥作用。在CNS之外，异常的T细胞活性也可能是ASD人群中基于免疫的疾病（如过敏、肠道炎症和自身免疫）发病率增加的原因。在本综述中，我们将讨论目前对ASD中T细胞生物学的理解，并推测其失调背后的机制。本综述还评估了异常的T细胞生物学在ASD背景下如何影响胃肠道问题和行为。
