Summary: Regulatory T cells (Tregs), usually tasked with immune system regulation, might also play a pivotal role in mood stabilization.
Controlled by the transcription factor Foxp3, any decrease in its expression has been linked to major depressive disorders. When Tregs were depleted in lab mice, they displayed heightened anxiety and depressive behaviors, which were reversed upon the restoration of Foxp3-expressing cells.
This suggests a potential link between immune responses, mood disorders, and even cognitive impairments as seen in Alzheimer’s disease.
Key Facts:
- Regulatory T cells (Tregs), controlled by Foxp3, may influence mood and cognitive function.
- Depleting Tregs in mice led to behaviors indicative of anxiety and depression.
- Cognitive impairments were observed in Alzheimer’s disease model mice when Tregs were depleted, implying an immune response connection to memory issues.
Source: PNAS Nexus
Regulatory T cells—work horses of the body’s immune system—may also stabilize mood, according to a study.
Forkhead box P3 (Foxp3) is a transcription factor that controls the production of regulatory T cells (Tregs). Tregs are key regulators of the adaptive immune system; however, previous work also suggests Tregs can influence mood. Decreased Foxp3 expression is associated with major depressive disorders.
Giulio Maria Pasinetti and colleagues tested a line of lab mice whose Tregs can be temporarily depleted on standard tasks designed to measure depression and anxiety in the rodents.
Treg-depleted mice were more likely to hide in darkness, moved less, and gave up on self-preservation actions more easily—suggesting that Treg-depleted mice were more anxious and depressed than control mice.
These neurobehavioral changes in Treg-depleted mice were reversed after restoration of Foxp3-expressing cells, and Treg-restored mice were more similar to controls than Treg-depleted mice were.
Additionally, mice bred to model Alzheimer’s disease showed cognitive impairments when their Tregs were depleted.
The authors posit that Treg depletion causes 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 cause anxiety, depression or Alzheimer’s disease-type cognitive deterioration, according to the authors.
About this neuroscience and psychology research news
Author: Giulio Maria Pasinetti
Source: PNAS Nexus
Contact: Giulio Maria Pasinetti – PNAS Nexus
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Transient anxiety and depression-like behaviors are linked to the depletion of Foxp3- expressing cells via inflammasome in the brain” by Giulio Maria Pasinetti et al. PNAS Nexus
Abstract
Transient anxiety and depression-like behaviors are linked to the depletion of Foxp3- expressing cells via inflammasome in the brain
Forkhead box P3 (Foxp3) is a transcription factor that influences functioning of regulatory T cells (Tregs) that modulate peripheral immune response.
Treg-mediated innate immunity and Treg-mediated adaptive immunity are receiving considerable attention for their implication in mechanisms associated with anxiety and depression.
Here, we demonstrated that depletion of Foxp3-expressing cells causally promotes transient anxiety- and depression-like behaviors associated with inflammasome activation in “depletion of regulatory T cell” (DEREG) mice.
We found that restoration of Foxp3-expressing cells causally reverses neurobehavioral changes through alteration of innate immune responses as assessed by caspase-1 activity and interleukin-1β (IL-1β) release in the hippocampal formation of DEREG mice.
Moreover, we found that depletion of Foxp3-expressing cells induces a significant elevation of granulocytes, monocytes, and macrophages in the blood, which are associated with transient expression of the matrix metalloprotease-9.
Similarly, we found that depletion of Foxp3-expressing cells in 5xFAD, a mouse model of Alzheimer’s disease (AD), exhibits elevated activated caspase-1 and promotion of IL-1β secretion and increased the level of amyloid-beta (Aβ)1–42 and Aβ plaque burden in the hippocampal formation that coincided with an acceleration of cognitive decline at a presymptomatic age in the 5xFAD mice.
Thus, our study provides evidence supporting the idea that Foxp3 may have a causal influence on peripheral immune responses. This, in turn, can promote an innate immune response within the brain, potentially leading to anxiety- and depression-like behaviors or cognitive decline.
