B cells are critical for autoimmune pathology in Scurfy mice
B cells are critical for autoimmune pathology in Scurfy mice
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DOI：
10.1073/pnas.1313547110
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发表时间：
2013-11-19
影响因子：
11.1
通讯作者：
Nimmerjahn, Falk
中科院分区：
文献类型：
--
作者：
Aschermann, Susanne;Lehmann, Christian H. K.;Nimmerjahn, Falk
调节性T细胞功能受损会导致一种严重的慢性自身免疫性疾病，影响皮屑病小鼠和人类的多个器官，并伴有免疫失调、多内分泌疾病、肠病、X-连锁(IPEX)综合征。以前的研究表明，T辅助细胞而不是细胞毒性T细胞对该病的病理至关重要。这种T细胞亚群是否直接导致组织炎症，或者更确切地说，通过与B细胞或髓系细胞的相互作用间接引起炎症，在很大程度上尚不清楚。为了研究这一点并确定这种致命疾病的潜在治疗靶点，我们调查了B细胞对这种复杂的自身免疫表型的贡献。我们发现B细胞和自身抗体的产生在皮肤、肝脏、肺和肾脏的炎症和B细胞的治疗性耗尽导致组织病理减轻和延长生存中起主要作用。相比之下，B细胞的缺失并没有影响系统T细胞的激活和高反应性，这表明B细胞产生的自身抗体可能是调节性T细胞缺陷小鼠自身免疫病理的主要因素。
Impaired regulatory T-cell function results in a severe chronic autoimmune disease affecting multiple organs in Scurfy mice and humans with the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Previous studies have shown that T helper cells but not cytotoxic T cells are critical for the disease pathology. Whether this T-cell subset is responsible directly for tissue inflammation or rather indirectly via the interaction with B cells or myeloid cells is largely unknown. To study this and to identify potential therapeutic targets for this lethal disease we investigated the contribution of B cells to this complex autoimmune phenotype. We show that B cells and the production of autoantibodies plays a major role for skin, liver, lung, and kidney inflammation and therapeutic depletion of B cells resulted in reduced tissue pathology and in prolonged survival. In contrast, the absence of B cells did not impact systemic T-cell activation and hyperreactivity, indicating that autoantibody production by B cells may be a major factor for the autoimmune pathology in mice deficient for regulatory T cells.