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Cited by 44T-cell and B-cell ImmunologyTryptophan and brain disordersGut microbiota and health

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

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Alvarez-Mon, Miguel Angel, Gomez-Lahoz, Ana Maria, Orozco, Arantxa, Lahera, Guillermo, Sosa-Reina, M. Dolores, Diaz, David, Albillos, Agustin, Quintero, Javier +3 more·2021·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2020.591962PMC PMC7820111
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Abstract

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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  • Recent evidence suggests the involvement of the immune system in several psychiatric conditions; one of the most studied in this respect is depression.

    “Recent evidence suggests the involvement of the immune system in several psychiatric conditions [203–205]; one of the most studied in this respect is depression [206–208].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [206]

    The Introduction (page unavailable) describes extensive research linking immune dysfunction with major depressive disorder, including consistent reports of elevated proinflammatory cytokines. It does not compare depression with other psychiatric conditions, so it does not establish that depression is one of the most studied in this respect. (LLM, conf=0.78)

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Authors
Alvarez-Mon, M. A., Gomez-Lahoz, A. M., Orozco, A., Lahera, G., Sosa-Reina, M. D., Diaz, D., Albillos, A., Quintero, J., Molero, P., Monserrat, J., & Alvarez-Mon, M.
Affiliations
  • Universidad de Alcalá (ES)
  • Hospital Universitario Príncipe de Asturias (ES)
  • Universidad Complutense de Madrid (ES)
  • Clinica Universidad de Navarra (ES)
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2021-01-08
Volume
11
Pages
591962-591962
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2020.591962
PMC
PMC7820111
OpenAlex
W3119265583
Cited by
44
References
11
Citations by year
2025: 6 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 5
FWCI
3.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • e_Buah (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Instituto de Salud Carlos III
  • Comunidad de Madrid
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
major depressive disorder, regulatory T cells, bacterial translocation, intestinal barrier dysfunction, CD4+ T cell differentiation, CCR2, CCR6, IL-10, zonulin, intestinal fatty acid binding protein, LPS-binding protein, gut microbiota, neuroinflammation

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