Tiziana Lorenzini, Wolfgang Faigle, Josefine Ruder, María José Docampo, Lennart Opitz, Roland Martin
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引用次数: 0
摘要
背景和目的:多发性硬化症(MS)被认为是中枢神经系统自身免疫性疾病的原型。它是导致青壮年慢性神经系统残疾的主要原因。促炎性 B 细胞和自身反应性 T 细胞在其发病机制中都扮演着重要角色。我们的目标是研究调节性 T 细胞(Tregs)的变化,它们可能也是该病的诱因,但其参与程度尚不明确:通过结合多种实验方法,我们对 41 名复发性多发性硬化症患者和 17 名健康供体的 Treg 区系进行了研究:结果:多发性硬化症患者的 CD4+ T 细胞和 Foxp3+ Tregs 数量减少,Treg 亚群的变化与年龄有关。接受纳他珠单抗治疗的患者的Treg抑制功能受到影响,而未接受治疗和接受抗CD20治疗的患者的Treg抑制功能不受影响。纳他珠单抗治疗患者的变化包括促炎细胞因子的增加和胸腺来源(t)-Tregs转录组的改变,而外周(p)-Tregs则没有:讨论:多发性硬化症患者的Treg功能障碍可能与t-Tregs转录组的改变和促炎环境有关。我们的发现有助于更好地了解多发性硬化症中的Tregs及其亚型。
Alterations of Thymus-Derived Tregs in Multiple Sclerosis.
Background and objectives: Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear.
Methods: By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors.
Results: Patients with MS showed a reduced frequency of CD4+ T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs.
Discussion: Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.
期刊介绍:
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.