Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

This study was supported by the British Heart Foundation (PG 09/002/ 2642). AJR is funded by King’s College London British Heart Foundation Centre of Excellence and EI was supported by the Department of Health via National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Tomas’ NHF Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. BG was supported by a British Heart Foundation studentship (FS/10/009/28166) and DC by an Arthritis Research UK Fellowship (18103)

Astrocytes modulate the polarization of CD4+ T cells to Th1 cells.

T-cell characteristics are dynamic and influenced by multiple factors. To test whether cells and the environment in the central nervous system (CNS) can influence T-cells, we tested if culturing mouse CD4(+) T-cells on mouse primary astrocytes, compared with standard feeder cells, modified T-cell polarization to Th1 and Treg subtypes. Astrocytes supported the production of Th1 cells and Tregs, which was diminished by inflammatory activation of astrocytes, and glutamate accumulation that may result from impaired glutamate uptake by astrocytes strongly promoted Th1 production. These results demonstrate that astrocytes and the environment in the CNS have the capacity to regulate T-cell characteristics

Immune Players in the CNS:The Astrocyte

<p>In the finely balanced environment of the central nervous system astrocytes, the most numerous cell type, play a role in regulating almost every physiological system. First found to regulate extracellular ions and pH, they have since been shown to regulate neurotransmitter levels, cerebral blood flow and energy metabolism. There is also growing evidence for an essential role of astrocytes in central immunity, which is the topic of this review. In the healthy state, the central nervous system is potently anti-inflammatory but under threat astrocytes readily respond to pathogens and to both sterile and pathogen-induced cell damage. In response, astrocytes take on some of the roles of immune cells, releasing cyto- and chemokines to influence effector cells, modulating the blood-brain barrier and forming glial scars. To date, much of the data supporting a role for astrocytes in immunity have been obtained from in vitro systems; however data from experimental models and clinical samples support the suggestion that astrocytes perform similar roles in more complex environments. This review will discuss some aspects of the role of astrocytes in central nervous system immunity.</p>