Table 2.
Mechanisms of Tregs in SAE.
| Pathogenesis mechanism | Main goal of the study | Disease model | Main outcome | Relevance in SAE | References |
|---|---|---|---|---|---|
| Imbalance/dysregulation of neurotransmitters | Role of acethylcoline (Ach) in the inflammatory response in survivors of sepsis, through activation or suppression of cholinergic transmission | Mice model of experimental sepsis induced by cecal-ligation and puncture (CLP) | Acethylcoline reduces inflammation, in the brain and spleen, by promoting the proliferation of Tregs and decreasing pro-inflammatory cytokines expression | Cholinergic anti-inflammatory pathway is the main pathway dysregulated in SAE and controls the inflammatory response and non-reflexive consciousness | (63) |
| Ischemic processes/injury | Therapeutic impact of allogenic adipose-derived exosomes (ADMSC) on the early targeting of inflammatory signaling and on the protection of the brain from sepsis syndrome-induced injury | Rat model of sepsis syndrome (SS)-induced by CLP (CLP) | Cell-derived exosomes (AMSCEXO) markedly suppress the systemic immune-inflammatory responses and protect the brain against SS-induced injury | Mesenchymal stem cell (MSC)-derived exosomes regulate the inflammatory-oxidative signaling axis and protect the organs from sepsis or ischemic-reperfusion damage | (10) |
| Cerebral endothelial cells activation | Explore the function of tissue-non-specific alkaline phosphatase (TNAP) at the brain-immune axis in experimental sepsis | Sublethal mice model of experimental sepsis induced by CLP | TNAP protects against the loss of BBB permeability and improves survival, clinical scores and behavioral outcomes associated with early sepsis | Alkaline phosphatases have a protective role at endothelial barriers and may shape the dynamic interactions within the brain-immune axis | (47) |
| Systemic immune-inflammation/cytokine storm; neuroinflammation; ischemic processes/injury; glial cells activation | Understand how immune cells, and more specifically T cells, influence SAE pathogenesis | Mice model of experimental sepsis induced by CLP | Tregs and Th2 infiltration resolves neuroinflammation and contributes for SAE attenuation and SAE-induced mental disorder | T cells infiltrating the brain during sepsis have an impact on the attenuation of specific SAE pathogenesis mechanisms and on the development and recovery of mental impairment in septic survivors | (12) |
Summary of the studies available, to date, evidencing the potential mechanisms by which Tregs may affect SAE pathogenesis.