Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Neurologic Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience Basel, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital of Basel, University of Basel, 4031 Basel, Switzerland.
Sci Immunol. 2020 Nov 20;5(53). doi: 10.1126/sciimmunol.abc7191.
Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.
肠道微生物组成的变化和 B 细胞的多种作用最近被牵连到多发性硬化症（MS）中，这是一种中枢神经系统（CNS）自身免疫性疾病。免疫球蛋白 A（IgA）是黏膜界面的关键调节剂。然而，肠道微生物群是否塑造了 IgA 反应，以及 IgA 细胞在神经炎症中的作用尚不清楚。在这里，我们确定了 MS 中的 IgA 结合分类群，并表明针对 MS 相关分类群的 IgA 产生细胞流向炎症性中枢神经系统，导致活跃 MS 和其他神经炎症性疾病中强烈的、分隔的 IgA 富集。与以前表征的多反应性抗共生 IgA 反应不同，中枢神经系统 IgA 与特定细菌菌株的表面结构发生交叉反应，但与脑组织不发生反应。这些发现确立了肠道微生物群特异性 IgA 细胞作为 MS 的系统介质，并表明黏膜 B 细胞在活跃的神经炎症中具有关键作用，这对 IgA 作为有信息价值的生物标志物和产生 IgA 的细胞作为免疫亚群用于治疗干预具有广泛的意义。
