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.
Neuroimmunomodulation

中文翻译：

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情绪障碍中的神经炎症：调节免疫细胞的作用

情绪障碍与慢性低度全身性（无菌）炎症有关，血浆中针对包括大脑在内的所有组织的促炎介质水平升高。重要的是，促炎细胞因子（例如，肿瘤坏死因子 α [TNF-α]、白介素 [IL]-6）通过影响神经递质水平、激活应激反应内分泌轴等作用来调节情绪行为和认知。然而，这种增强炎症的潜在机制尚不清楚。越来越多的证据表明，受损的免疫调节机制可能在这种情况下发挥作用。患有情绪障碍（重度抑郁症 [MDD] 和双相情感障碍 [BD]）的患者的先天性（自然杀伤调节细胞和骨髓源性抑制细胞 [MDSCs]）和适应性免疫反应（CD4 ⁺ CD25 ）的主要调节细胞数量减少⁺ FoxP3 ⁺, B 调节细胞）。功能失调的调节性免疫细胞可能通过不同机制导致在情绪障碍中观察到的全身和神经炎症，例如：(i) 未能产生足够的压力相关反应，(ii) 通过小胶质细胞激活间接，(iii) 缺乏营养支持和亲- 大脑中 T 细胞的认知功能，以及 (iv) 生态失调。总之，适应不良的免疫调节机制似乎与情绪障碍的发生和进展有关。更深入地了解这些机制可能会导致新的治疗策略的发展。
神经免疫调节