Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells

Moisés E. Bauer, Antônio L. Teixeira

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

Mood disorders are associated with chronic low-grade systemic (sterile) inflammation, with increased plasma levels of pro-inflammatory mediators targeting all tissues including the brain. Importantly, pro-inflammatory cytokines (ex., tumor-necrosis factor alpha [TNF-α], interleukin [IL]-6) regulate mood behavior and cognition by influencing neurotransmitter levels, activating stress-responsive endocrine axes, among other effects. However, the mechanisms underlying this enhanced inflammation are not well understood. There is increasing evidence indicating that impaired immunoregulatory mechanisms may play a role in this context. Patients with mood disorders (major depression [MDD] and bipolar disorder [BD]) have reduced numbers of major regulatory cells of both innate (natural killer regulatory cells and myeloid-derived suppressor cells [MDSCs]) and adaptive immune responses (CD4+CD25+FoxP3+, B regulatory cells). Dysfunctional regulatory immune cells might contribute to systemic and neuroinflammation observed in mood disorders via different mechanisms, such as: (i) failure to develop adequate stress-related responses, (ii) indirectly through microglial activation, (iii) lack of trophic support and pro-cognitive functions of T cells in the brain, and (iv) dysbiosis. In conclusion, maladaptive immunoregulatory mechanisms seem to be involved with both onset and progression of mood disorders. A deeper understanding of these mechanisms may lead to the development of new therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)99-107
Number of pages9
JournalNeuroImmunoModulation
Volume28
Issue number3
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

Keywords

  • Bipolar disorder
  • Cytokines
  • Inflammation
  • Major depressive disorder
  • Neuroinflammation
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems

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