Bauer Moisés E, Teixeira Antônio L
Laboratory of Immunobiology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
National Institute of Science and Technology - Neuroimmunomodulation (INCT-NIM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, Brazil.
Neuroimmunomodulation. 2021;28(3):99-107. doi: 10.1159/000515594. Epub 2021 May 5.
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.
情绪障碍与慢性低度全身性（无菌性）炎症相关，血浆中促炎介质水平升高，这些介质作用于包括大脑在内的所有组织。重要的是，促炎细胞因子（例如，肿瘤坏死因子α [TNF-α]、白细胞介素 [IL]-6）通过影响神经递质水平、激活应激反应内分泌轴等方式来调节情绪行为和认知。然而，这种炎症增强背后的机制尚未完全明确。越来越多的证据表明，免疫调节机制受损可能在这一过程中发挥作用。患有情绪障碍（重度抑郁症 [MDD] 和双相情感障碍 [BD]）的患者，其固有免疫（自然杀伤调节细胞和髓系来源的抑制细胞 [MDSCs]）和适应性免疫反应（CD4+CD25+FoxP3+、B 调节细胞）的主要调节细胞数量均减少。功能失调的调节性免疫细胞可能通过不同机制导致情绪障碍中出现的全身性和神经炎症，例如：（i）无法产生适当的应激相关反应；（ii）通过小胶质细胞激活间接导致；（iii）大脑中 T 细胞缺乏营养支持和促认知功能；（iv）微生物群失调。总之，适应不良的免疫调节机制似乎与情绪障碍的发生和发展都有关。对这些机制的更深入理解可能会带来新治疗策略的开发。
