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Review ArticleReview Article

Targeting the Adaptive Immune System in Depression: Focus on T Helper 17 Cells

Eléonore Beurel, Eva M. Medina-Rodriguez and Richard S. Jope
Robert Dantzer, ASSOCIATE EDITOR
Pharmacological Reviews April 2022, 74 (2) 373-386; DOI: https://doi.org/10.1124/pharmrev.120.000256
Eléonore Beurel
Department of Psychiatry and Behavioral Sciences (E.B., E.M.M.-R., R.S.J.) and Department of Biochemistry and Molecular Biology Miller School of Medicine (E.B., R.S.J.), University of Miami, Miami, Florida and Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida (E.M.M.-R., R.S.J.)
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Eva M. Medina-Rodriguez
Department of Psychiatry and Behavioral Sciences (E.B., E.M.M.-R., R.S.J.) and Department of Biochemistry and Molecular Biology Miller School of Medicine (E.B., R.S.J.), University of Miami, Miami, Florida and Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida (E.M.M.-R., R.S.J.)
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Richard S. Jope
Department of Psychiatry and Behavioral Sciences (E.B., E.M.M.-R., R.S.J.) and Department of Biochemistry and Molecular Biology Miller School of Medicine (E.B., R.S.J.), University of Miami, Miami, Florida and Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida (E.M.M.-R., R.S.J.)
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Robert Dantzer
Department of Psychiatry and Behavioral Sciences (E.B., E.M.M.-R., R.S.J.) and Department of Biochemistry and Molecular Biology Miller School of Medicine (E.B., R.S.J.), University of Miami, Miami, Florida and Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, Florida (E.M.M.-R., R.S.J.)
Roles: ASSOCIATE EDITOR
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Abstract

There is a vital need to understand mechanisms contributing to susceptibility to depression to improve treatments for the 11% of Americans who currently suffer from this debilitating disease. The adaptive immune system, comprising T and B cells, has emerged as a potential contributor to depression, as demonstrated in the context of lymphopenic mice. Overall, patients with depression have reduced circulating T and regulatory B cells, "immunosuppressed" T cells, and alterations in the relative abundance of T cell subtypes. T helper (Th) cells have the capacity to differentiate to various lineages depending on the cytokine environment, antigen stimulation, and costimulation. Regulatory T cells are decreased, and the Th1/Th2 ratio and the Th17 cells are increased in patients with depression. Evidence for changes in each Th lineage has been reported to some extent in patients with depression. However, the evidence is strongest for the association of depression with changes in Th17 cells. Th17 cells produce the inflammatory cytokine interleukin (IL)-17A, and the discovery of Th17 cell involvement in depression evolved from the well established link that IL-6, which is required for Th17 cell differentiation, contributes to the onset, and possibly maintenance, of depression. One intriguing action of Th17 cells is their participation in the gut-brain axis to mediate stress responses. Although the mechanisms of action of Th17 cells in depression remain unclear, neutralization of IL-17A by anti-IL-17A antibodies, blocking stress-induced production, or release of gut Th17 cells represent feasible therapeutic approaches and might provide a new avenue to improve depression symptoms.

Significance Statement Th17 cells appear as a promising therapeutic target for depression, for which efficacious therapeutic options are limited. The use of neutralizing antibodies targeting Th17 cells has provided encouraging results in depressed patients with comorbid autoimmune diseases.

Footnotes

  • The work was supported by National Institutes of Health National Institute of Mental Health [Grant R01-MH104656] and [Grant R01-MH110415] (to E.B.) and by a Merit Award from the Veterans Administration [BX003678] (to R.S.J.).

  • No author has an actual or perceived conflict of interest with the contents of this article.

  • https://doi.org/10.1124/pharmrev.120.000256.

  • Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 74 (2)
Pharmacological Reviews
Vol. 74, Issue 2
1 Apr 2022
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Review ArticleReview Article

Adaptive Immune System and Depression

Eléonore Beurel, Eva M. Medina-Rodriguez and Richard S. Jope
Pharmacological Reviews April 1, 2022, 74 (2) 373-386; DOI: https://doi.org/10.1124/pharmrev.120.000256

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Review ArticleReview Article

Adaptive Immune System and Depression

Eléonore Beurel, Eva M. Medina-Rodriguez and Richard S. Jope
Pharmacological Reviews April 1, 2022, 74 (2) 373-386; DOI: https://doi.org/10.1124/pharmrev.120.000256
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  • Article
    • Abstract
    • Introduction
    • I. Dysregulation of the Adaptive Immune Response in Depression
    • II. Possible Origins of These Immune Dysregulations in Depression
    • III. Implications for Patients with Depression
    • IV. Conclusion
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