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.)
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.).
Pharmacol Rev. 2022 Apr;74(2):373-386. doi: 10.1124/pharmrev.120.000256.
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.
了解导致易患抑郁症的机制对于改善目前 11%的美国人的治疗方法至关重要，他们正在遭受这种使人衰弱的疾病。适应性免疫系统，包括 T 和 B 细胞，已被证明是抑郁症的潜在致病因素，尤其是在淋巴缺乏的小鼠中。总的来说，患有抑郁症的患者循环 T 和调节性 B 细胞减少，“免疫抑制”T 细胞，以及 T 细胞亚型的相对丰度改变。T 辅助（Th）细胞能够根据细胞因子环境、抗原刺激和共刺激而分化为各种谱系。调节性 T 细胞减少，Th1/Th2 比值和 Th17 细胞增加在抑郁症患者中。在一定程度上，抑郁症患者的每种 Th 谱系都有改变的证据。然而，与 Th17 细胞改变相关的证据最为有力。Th17 细胞产生炎症细胞因子白细胞介素（IL）-17A，Th17 细胞参与抑郁症的发现源于已确立的关联，即 IL-6 是 Th17 细胞分化所必需的，有助于抑郁症的发作，可能还有维持。Th17 细胞的一个有趣作用是它们参与肠道-大脑轴来介导应激反应。尽管 Th17 细胞在抑郁症中的作用机制尚不清楚，但抗 IL-17A 抗体中和 IL-17A、阻断应激诱导的产生或释放肠道 Th17 细胞代表了可行的治疗方法，可能为改善抑郁症症状提供新途径。意义：Th17 细胞似乎是治疗抑郁症的一个有希望的治疗靶点，而治疗抑郁症的有效治疗方法有限。针对 Th17 细胞的中和抗体的使用在患有合并自身免疫性疾病的抑郁患者中提供了令人鼓舞的结果。
