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Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells
Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have b...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124178/ https://www.ncbi.nlm.nih.gov/pubmed/35597802 http://dx.doi.org/10.1038/s41598-022-12464-2 |
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author | Rivet-Noor, Courtney R. Merchak, Andrea R. Li, Sihan Beiter, Rebecca M. Lee, Sangwoo Thomas, Jalon Aaron Fernández-Castañeda, Anthony Shin, Jung-Bum Gaultier, Alban |
author_facet | Rivet-Noor, Courtney R. Merchak, Andrea R. Li, Sihan Beiter, Rebecca M. Lee, Sangwoo Thomas, Jalon Aaron Fernández-Castañeda, Anthony Shin, Jung-Bum Gaultier, Alban |
author_sort | Rivet-Noor, Courtney R. |
collection | PubMed |
description | Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (Ahr) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORγt + CD4 + Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the Ahr, Th17s and depression remains critical to understanding mood disorders. Here, we utilize genetic knockouts to examine the role of the microbial sensor Ahr in the development of stressinduced despair behavior. We observe an Ahr-independent increase in gut-associated Th17s in stressed mice, indicating that the Ahr is not responsible for this communication. Further, we utilized a CD4-specific RAR Related Orphan Receptor C (Rorc) knockout line to disrupt the production of Th17s. Mice lacking Rorc-produced IL-17 did not show any differences in behavior before or after stress when compared to controls. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed by traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety- or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression. |
format | Online Article Text |
id | pubmed-9124178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91241782022-05-23 Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells Rivet-Noor, Courtney R. Merchak, Andrea R. Li, Sihan Beiter, Rebecca M. Lee, Sangwoo Thomas, Jalon Aaron Fernández-Castañeda, Anthony Shin, Jung-Bum Gaultier, Alban Sci Rep Article Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (Ahr) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORγt + CD4 + Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the Ahr, Th17s and depression remains critical to understanding mood disorders. Here, we utilize genetic knockouts to examine the role of the microbial sensor Ahr in the development of stressinduced despair behavior. We observe an Ahr-independent increase in gut-associated Th17s in stressed mice, indicating that the Ahr is not responsible for this communication. Further, we utilized a CD4-specific RAR Related Orphan Receptor C (Rorc) knockout line to disrupt the production of Th17s. Mice lacking Rorc-produced IL-17 did not show any differences in behavior before or after stress when compared to controls. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed by traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety- or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression. Nature Publishing Group UK 2022-05-21 /pmc/articles/PMC9124178/ /pubmed/35597802 http://dx.doi.org/10.1038/s41598-022-12464-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rivet-Noor, Courtney R. Merchak, Andrea R. Li, Sihan Beiter, Rebecca M. Lee, Sangwoo Thomas, Jalon Aaron Fernández-Castañeda, Anthony Shin, Jung-Bum Gaultier, Alban Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title | Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title_full | Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title_fullStr | Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title_full_unstemmed | Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title_short | Stress-induced despair behavior develops independently of the Ahr-RORγt axis in CD4 + cells |
title_sort | stress-induced despair behavior develops independently of the ahr-rorγt axis in cd4 + cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124178/ https://www.ncbi.nlm.nih.gov/pubmed/35597802 http://dx.doi.org/10.1038/s41598-022-12464-2 |
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