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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...

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Autores principales: Yang, Eun-Jeong, Rahim, Md Al, Griggs, Elizabeth, Iban-Arias, Ruth, Pasinetti, Giulio Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443660/
https://www.ncbi.nlm.nih.gov/pubmed/37614669
http://dx.doi.org/10.1093/pnasnexus/pgad251
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author Yang, Eun-Jeong
Rahim, Md Al
Griggs, Elizabeth
Iban-Arias, Ruth
Pasinetti, Giulio Maria
author_facet Yang, Eun-Jeong
Rahim, Md Al
Griggs, Elizabeth
Iban-Arias, Ruth
Pasinetti, Giulio Maria
author_sort Yang, Eun-Jeong
collection PubMed
description 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.
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spelling pubmed-104436602023-08-23 Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain Yang, Eun-Jeong Rahim, Md Al Griggs, Elizabeth Iban-Arias, Ruth Pasinetti, Giulio Maria PNAS Nexus Biological, Health, and Medical Sciences 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. Oxford University Press 2023-08-22 /pmc/articles/PMC10443660/ /pubmed/37614669 http://dx.doi.org/10.1093/pnasnexus/pgad251 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Biological, Health, and Medical Sciences
Yang, Eun-Jeong
Rahim, Md Al
Griggs, Elizabeth
Iban-Arias, Ruth
Pasinetti, Giulio Maria
Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title_full Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title_fullStr Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title_full_unstemmed Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title_short Transient anxiety-and depression-like behaviors are linked to the depletion of Foxp3-expressing cells via inflammasome in the brain
title_sort transient anxiety-and depression-like behaviors are linked to the depletion of foxp3-expressing cells via inflammasome in the brain
topic Biological, Health, and Medical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443660/
https://www.ncbi.nlm.nih.gov/pubmed/37614669
http://dx.doi.org/10.1093/pnasnexus/pgad251
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