Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease.
Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease.
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DOI：
10.1172/jci.insight.158153
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发表时间：
2022-06-22
期刊：
影响因子：
8
通讯作者：
Segal, Benjamin M.
中科院分区：
文献类型：
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作者：
Atkinson, Jeffrey R.;Jerome, Andrew D.;Sas, Andrew R.;Munie, Ashley;Wang, Cankun;Ma, Anjun;Arnold, William D.;Segal, Benjamin M.
生物老化是与多发性硬化症（MS）临床表型相关的最强因素。复发缓解型MS通常在第三或第四个十年出现，而进行性MS（PMS）的平均出现年龄为45岁。在这里，我们表明，实验性自身免疫性脑脊髓炎（EAE），诱导过继转移致脑炎的CD4+ Th17细胞，是更严重的，不太可能缓解，在中年与年轻的成年小鼠相比。在老年小鼠的CNS浸润中，供体T细胞和中性粒细胞更丰富，而B细胞相对稀疏。与互惠骨髓嵌合体的实验表明，放射抗性，非造血细胞发挥了主导作用，在EAE的神经炎症反应的年龄依赖性功能的形成，以及临床过程中。与经前综合征类似，中年过继移植受者的EAE的特征是广泛的小胶质细胞激活。来自老年小鼠的小胶质细胞表达了一种独特的转录组学特征，提示增强的趋化因子合成和抗原呈递。总的来说，我们的研究结果表明，抑制小胶质细胞活化以及衰老相关特性的获得或表达的药物可能有助于治疗进行性炎症性脱髓鞘疾病。
Biological aging is the strongest factor associated with the clinical phenotype of multiple sclerosis (MS). Relapsing-remitting MS typically presents in the third or fourth decade, whereas the mean age of presentation of progressive MS (PMS) is 45 years old. Here, we show that experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of encephalitogenic CD4+ Th17 cells, was more severe, and less likely to remit, in middle-aged compared with young adult mice. Donor T cells and neutrophils were more abundant, while B cells were relatively sparse, in CNS infiltrates of the older mice. Experiments with reciprocal bone marrow chimeras demonstrated that radio-resistant, nonhematopoietic cells played a dominant role in shaping age-dependent features of the neuroinflammatory response, as well as the clinical course, during EAE. Reminiscent of PMS, EAE in middle-aged adoptive transfer recipients was characterized by widespread microglial activation. Microglia from older mice expressed a distinctive transcriptomic profile suggestive of enhanced chemokine synthesis and antigen presentation. Collectively, our findings suggest that drugs that suppress microglial activation, and acquisition or expression of aging-associated properties, may be beneficial in the treatment of progressive forms of inflammatory demyelinating disease.
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影响因子：
6.2
作者：
Clark, Kareem C.;Josephson, Anna;Dupree, Jeffrey L.
通讯作者：
Dupree, Jeffrey L.
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth
影响因子：
64.5
作者：
Duscha, Alexander;Gisevius, Barbara;Haghikia, Aiden
通讯作者：
Haghikia, Aiden
GM-CSF通过改变中枢神经系统渗透细胞的组成来促进实验性自身免疫性脑脊髓炎的慢性残疾，但可用于疾病诱导。
DOI：
10.4049/jimmunol.1701484
发表时间：
2018-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Duncker PC;Stoolman JS;Huber AK;Segal BM
通讯作者：
Segal BM
影响因子：
6.2
作者：
通讯作者：
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