| First Author | Yang EJ | Year | 2023 |
| Journal | PNAS Nexus | Volume | 2 |
| Issue | 8 | Pages | pgad251 |
| PubMed ID | 37614669 | Mgi Jnum | J:350201 |
| Mgi Id | MGI:7661171 | Doi | 10.1093/pnasnexus/pgad251 |
| Citation | Yang EJ, et al. (2023) Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain. PNAS Nexus 2(8):pgad251 |
| abstractText | 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-1beta (IL-1beta) 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-1beta secretion and increased the level of amyloid-beta (Abeta)(1-42) and Abeta 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. |
