T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives.
T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives.
复制标题
DOI：
10.1016/j.bbih.2021.100330
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Del-Ben CM
中科院分区：
文献类型：
--
作者：
Corsi-Zuelli F;Deakin B;de Lima MHF;Qureshi O;Barnes NM;Upthegrove R;Louzada-Junior P;Del-Ben CM
许多研究报告说，精神病患者，甚至在药物治疗之前，血液细胞因子水平相对于健康对照者有轻度升高。相比之下，研究精神病中免疫功能和细胞因子变化的细胞基础的研究却非常缺乏。少数流式细胞术研究仅限于计数主要类别的单核细胞和淋巴细胞的比例，而没有区分它们的促炎和抗炎亚群。此外，大多数调查是横断面的，并且是对长期用药的患者进行的。这些特征使得很难消除生活方式因素、疾病持续时间和长期服用抗精神病药物引起的疾病相关变化的混淆。本文的重点是调节性T细胞（Tregs），调节先天和适应性免疫力量以及星形胶质细胞和小胶质细胞之间的神经免疫相互作用的基础免疫细胞。Tregs也与心脏代谢紊乱有关，这是精神病的常见合并症。我们最近提出，在我们的临床发现和其他独立研究的推动下，treg是精神病的功能低下（' h- treg '）。我们的h- treg神经胶质失衡假说为全身性免疫失调和精神病发展机制的共同发生提供了一个新的解释。本文扩展了我们最近的综述，即h-Treg假说，涵盖了基于treg的临床前研究发现及其临床意义的新发现。我们提供了精神病Treg研究的详细特征，确定了重要的方法局限性和科学创新的观点。本文提出的结果重申了我们提出的精神病中的h-Treg状态，并揭示了新的临床前研究表明treg增强疗法的潜在益处。显然需要对drug-naïve或最低限度治疗的患者进行纵向研究，使用更复杂的技术，如流式细胞术、CyTOF表达标记和体外共培养试验，以正式测试Tregs的抑制能力。对Treg研究的投资为针对个人特异性免疫失调的新兴免疫调节治疗方式提供了主要的潜在益处。treg是控制先天和适应性免疫平衡的基础免疫细胞。Tregs调节星形胶质细胞-小胶质细胞的神经免疫相互作用。临床和实验研究表明，Tregs在精神病中功能低下，这可能解释精神病中的炎症和神经胶质功能障碍。对Treg研究的投资将有助于揭示精神病的新机制。treg增强疗法可以指导精神病的个性化治疗。
Many studies have reported that patients with psychosis, even before drug treatment, have mildly raised levels of blood cytokines relative to healthy controls. In contrast, there is a remarkable scarcity of studies investigating the cellular basis of immune function and cytokine changes in psychosis. The few flow-cytometry studies have been limited to counting the proportion of the major classes of monocyte and lymphocytes without distinguishing their pro- and anti-inflammatory subsets. Moreover, most of the investigations are cross-sectional and conducted with patients on long-term medication. These features make it difficult to eliminate confounding of illness-related changes by lifestyle factors, disease duration, and long exposure to antipsychotics. This article focuses on regulatory T cells (Tregs), cornerstone immune cells that regulate innate and adaptive immune forces and neuroimmune interactions between astrocytes and microglia. Tregs are also implicated in cardio-metabolic disorders that are common comorbidities of psychosis. We have recently proposed that Tregs are hypofunctional (‘h-Tregs’) in psychosis driven by our clinical findings and other independent research. Our h-Treg-glial imbalance hypothesis offers a new account for the co-occurrence of systemic immune dysregulation and mechanisms of psychosis development. This article extends our recent review, the h-Treg hypothesis, to cover new discoveries on Treg-based therapies from pre-clinical findings and their clinical implications. We provide a detailed characterisation of Treg studies in psychosis, identifying important methodological limitations and perspectives for scientific innovation. The outcomes presented in this article reaffirms our proposed h-Treg state in psychosis and reveals emerging preclinical research suggesting the potential benefit of Treg-enhancing therapies. There is a clear need for longitudinal studies conducted with drug-naïve or minimally treated patients using more sophisticated techniques of flow-cytometry, CyTOF expression markers, and in vitro co-culture assays to formally test the suppressive capacity of Tregs. Investment in Treg research offers major potential benefits in targeting emerging immunomodulatory treatment modalities on person-specific immune dysregulations. Tregs are cornerstone immune cells controlling the innate and adaptive immune balance. Tregs regulate astrocytic-microglial neuroimmune interactions. Clinical and experimental research suggest that Tregs are hypofunctional in psychosis, which may explain inflammation and glial dysfunction in psychosis . Investment in Treg research will help to uncover novel mechanisms in psychosis. Treg-enhancing therapies may guide personalised treatments in psychosis.
登录
查看更多内容
影响因子：
7.3
作者：
Duggleby R;Danby RD;Madrigal JA;Saudemont A
通讯作者：
Saudemont A
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
6.8
作者：
Chaudhry IB;Husain MO;Khoso AB;Husain MI;Buch MH;Kiran T;Fu B;Bassett P;Qurashi I;Ur Rahman R;Baig S;Kazmi A;Corsi-Zuelli F;Haddad PM;Deakin B;Husain N
通讯作者：
Husain N
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
3.9
作者：
Avdeeva, Anastasia;Rubtsov, Yury;Nasonov, Eugene
通讯作者：
Nasonov, Eugene