Summary
Regulatory T cells (Tregs), generally responsible for immune system regulation, might also play a key role in mood stabilization. Controlled by the transcription factor Foxp3, a reduction in its expression has been associated with major depressive disorders. Experiments with lab mice demonstrated that depletion of Tregs led to increased anxiety and depressive behaviors, which were reversed when Foxp3-expressing cells were restored. This suggests a potential connection between immune responses, mood disorders, and cognitive impairments such as those observed in Alzheimer’s disease.
Key Facts
- Regulatory T cells (Tregs), regulated by Foxp3, may influence mood and cognitive function.
- A decrease in Tregs in mice resulted in behaviors indicative of anxiety and depression.
- When Tregs were depleted in mice bred to model Alzheimer’s disease, cognitive impairments were observed, implying an immune response connection to memory issues.
Detailed Study Information
A recent study indicates that Regulatory T cells, part of the body’s immune system, may also help regulate mood. The transcription factor Foxp3 controls the production of Tregs. Tregs are crucial regulators of the adaptive immune system, and previous work suggests they can influence mood as well. Lowered Foxp3 expression has been linked to major depressive disorders.
Giulio Maria Pasinetti and his team tested a group of lab mice whose Tregs could be temporarily depleted. Treg-depleted mice exhibited increased signs of anxiety and depression, being more likely to hide in darkness, move less, and give up on self-preservation actions more easily compared to control mice. These neurobehavioral changes were reversed after restoring Foxp3-expressing cells. Treg depletion also caused proliferation of peripheral immune cells, some of which can cross the blood-brain barrier into the brain and cause inflammatory responses in the hippocampal formation. This transient activation of innate immunity in the brain can potentially cause anxiety, depression, or cognitive deterioration similar to Alzheimer’s disease, according to the authors.
About This Study
Giulio Maria Pasinetti is the author of this study. The study was published in PNAS Nexus. The image credit goes to Neuroscience News. The original research is open access and titled “Transient anxiety and depression-like behaviors are linked to the depletion of Foxp3- expressing cells via inflammasome in the brain”, authored by Giulio Maria Pasinetti et al. in PNAS Nexus.
Abstract
The study focuses on Forkhead box P3 or Foxp3, a transcription factor that influences the functions of regulatory T cells or Tregs, known to modulate the peripheral immune response. Treg-mediated innate and adaptive immunities have been considered important for their implications in the mechanisms associated with anxiety and depression. In this study, depletion of Foxp3-expressing cells has been observed to cause transient anxiety- and depression-like behaviors, which are associated with inflammasome activation in “depletion of regulatory T cell” (DEREG) mice.
My personal opinion, as a psychiatrist, is that this study holds great potential for understanding the neurobiological underpinnings of cognitive and mood disorders. If the role of Tregs in modulating mood is confirmed, it may open new avenues for therapeutic interventions.
Dr Michael Thomas Williams, MD, Cure of Mind