Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma.
Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma.
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DOI：
10.1038/s41467-018-05681-9
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发表时间：
2018-08-10
影响因子：
16.6
通讯作者：
Chen DF
中科院分区：
文献类型：
--
作者：
Chen H;Cho KS;Vu THK;Shen CH;Kaur M;Chen G;Mathew R;McHam ML;Fazelat A;Lashkari K;Au NPB;Tse JKY;Li Y;Yu H;Yang L;Stein-Streilein J;Ma CHE;Woolf CJ;Whary MT;Jager MJ;Fox JG;Chen J;Chen DF
青光眼是世界范围内最常见的神经退行性疾病，也是导致失明的主要原因。引起昏迷性神经退行性变的机制还不完全清楚。在这里，我们表明，使用小鼠缺乏T和/或B细胞和过继细胞转移，瞬时升高眼内压（IOP）足以诱导T细胞浸润到视网膜。这种T细胞浸润导致视网膜神经节细胞变性的延长阶段，其在IOP恢复到正常水平后持续存在。热休克蛋白（HSP）被鉴定为青光眼患者和青光眼小鼠T细胞反应的靶抗原。此外，视网膜浸润性T细胞与人类和细菌热休克蛋白交叉反应;在缺乏肠道微生物菌群的情况下饲养的小鼠不会产生昏迷性T细胞反应或相关的神经变性。这些结果提供了令人信服的证据表明，昏迷性神经变性部分是由暴露于肠道微生物菌群而预致敏的T细胞介导的。青光眼是一种神经退行性疾病，其病因尚不清楚。在这里，作者表明，眼内压升高诱导T细胞浸润的眼睛。此外，他们还表明内源性抗原和自体抗原之间的T细胞交叉反应性有助于小鼠的疾病发作。
Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora. Glaucoma is a neurodegenerative disease of which the etiology is still unclear. Here the authors show that elevation of intraocular pressure induces T cell infiltration in the eyes. Furthermore, they show that T cell cross-reactivity between endogenous and commensal antigens contributes to disease onset in mice.