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Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kin...

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Autores principales: Alvarez-Mon, Miguel Angel, Gomez-Lahoz, Ana Maria, Orozco, Arantxa, Lahera, Guillermo, Sosa-Reina, M. Dolores, Diaz, David, Albillos, Agustin, Quintero, Javier, Molero, Patricio, Monserrat, Jorge, Alvarez-Mon, Melchor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820111/
https://www.ncbi.nlm.nih.gov/pubmed/33488424
http://dx.doi.org/10.3389/fpsyt.2020.591962
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author Alvarez-Mon, Miguel Angel
Gomez-Lahoz, Ana Maria
Orozco, Arantxa
Lahera, Guillermo
Sosa-Reina, M. Dolores
Diaz, David
Albillos, Agustin
Quintero, Javier
Molero, Patricio
Monserrat, Jorge
Alvarez-Mon, Melchor
author_facet Alvarez-Mon, Miguel Angel
Gomez-Lahoz, Ana Maria
Orozco, Arantxa
Lahera, Guillermo
Sosa-Reina, M. Dolores
Diaz, David
Albillos, Agustin
Quintero, Javier
Molero, Patricio
Monserrat, Jorge
Alvarez-Mon, Melchor
author_sort Alvarez-Mon, Miguel Angel
collection PubMed
description Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation. Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3(+) Tregs and their distribution on the naïve (T(N)), effector (T(E)), central (T(CM)), and effector memory(T(EM)) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay. Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the T(N), T(E), T(CM), and T(EM) stages. The percentage of Tregs cells at T(N) stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients. Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25(high)FoxP3(+) and CD25(low)FoxP3(+) subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.
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spelling pubmed-78201112021-01-23 Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder Alvarez-Mon, Miguel Angel Gomez-Lahoz, Ana Maria Orozco, Arantxa Lahera, Guillermo Sosa-Reina, M. Dolores Diaz, David Albillos, Agustin Quintero, Javier Molero, Patricio Monserrat, Jorge Alvarez-Mon, Melchor Front Psychiatry Psychiatry Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation. Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3(+) Tregs and their distribution on the naïve (T(N)), effector (T(E)), central (T(CM)), and effector memory(T(EM)) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay. Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the T(N), T(E), T(CM), and T(EM) stages. The percentage of Tregs cells at T(N) stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients. Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25(high)FoxP3(+) and CD25(low)FoxP3(+) subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7820111/ /pubmed/33488424 http://dx.doi.org/10.3389/fpsyt.2020.591962 Text en Copyright © 2021 Alvarez-Mon, Gomez-Lahoz, Orozco, Lahera, Sosa-Reina, Diaz, Albillos, Quintero, Molero, Monserrat and Alvarez-Mon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Alvarez-Mon, Miguel Angel
Gomez-Lahoz, Ana Maria
Orozco, Arantxa
Lahera, Guillermo
Sosa-Reina, M. Dolores
Diaz, David
Albillos, Agustin
Quintero, Javier
Molero, Patricio
Monserrat, Jorge
Alvarez-Mon, Melchor
Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title_full Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title_fullStr Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title_full_unstemmed Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title_short Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder
title_sort blunted expansion of regulatory t lymphocytes is associated with increased bacterial translocation in patients with major depressive disorder
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820111/
https://www.ncbi.nlm.nih.gov/pubmed/33488424
http://dx.doi.org/10.3389/fpsyt.2020.591962
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