Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Center for Research in Transplantation and Translational Immunology, Nantes Université, CHU Nantes, INSERM, UMR 1064, Nantes, France.
Immunol Rev. 2022 Oct;311(1):151-176. doi: 10.1111/imr.13122. Epub 2022 Jul 31.
Inflammation is a biological process that dynamically alters the surrounding microenvironment, including participating immune cells. As a well-protected organ surrounded by specialized barriers and with immune privilege properties, the central nervous system (CNS) tightly regulates immune responses. Yet in neuroinflammatory conditions, pathogenic immunity can disrupt CNS structure and function. T cells in particular play a key role in promoting and restricting neuroinflammatory responses, while the inflamed CNS microenvironment can influence and reshape T cell function and identity. Still, the contraction of aberrant T cell responses within the CNS is not well understood. Using autoimmunity as a model, here we address the contribution of CD4 T helper (Th) cell subsets in promoting neuropathology and disease. To address the mechanisms antagonizing neuroinflammation, we focus on the control of the immune response by regulatory T cells (Tregs) and describe the counteracting processes that preserve their identity under inflammatory challenges. Finally, given the influence of the local microenvironment on immune regulation, we address how CNS-intrinsic signals reshape T cell function to mitigate abnormal immune T cell responses.
炎症是一种动态改变周围微环境的生物学过程,包括参与免疫细胞。作为一个被专门的屏障所保护的器官,具有免疫特权特性,中枢神经系统(CNS)严格调节免疫反应。然而,在神经炎症情况下,致病性免疫可能会破坏中枢神经系统的结构和功能。T 细胞在促进和限制神经炎症反应中起着关键作用,而炎症中枢神经系统微环境可以影响和重塑 T 细胞的功能和特性。然而,中枢神经系统内异常 T 细胞反应的收缩还不是很清楚。我们利用自身免疫作为模型,在这里探讨 CD4 辅助性 T 细胞(Th)亚群在促进神经病理学和疾病中的作用。为了研究对抗神经炎症的机制,我们专注于调节性 T 细胞(Tregs)对免疫反应的控制,并描述在炎症挑战下维持其特性的拮抗过程。最后,鉴于局部微环境对免疫调节的影响,我们探讨了中枢神经系统内在信号如何重塑 T 细胞功能,以减轻异常免疫 T 细胞反应。