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Peripherally-sourced myeloid antigen presenting cells increase with advanced aging
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.bbi.2020.08.023
Pedram Honarpisheh 1 , Frank W Blixt 1 , Maria P Blasco Conesa 1 , William Won 1 , John d'Aigle 1 , Yashasvee Munshi 1 , Jacob Hudobenko 2 , J Weldon Furr 1 , Alexis Mobley 1 , Juneyoung Lee 1 , Katherine E Brannick 3 , Liang Zhu 4 , Amy L Hazen 5 , Robert M Bryan 6 , Louise D McCullough 1 , Bhanu P Ganesh 1
Affiliation  

Aging is associated with dysfunction of the gut microbiota-immune-brain axis, a major regulatory axis in both brain health and in central nervous system (CNS) diseases. Antigen presenting cells (APCs) play a major role in sensing changes in the gut microbiota and regulation of innate and adaptive immune responses. APCs have also been implicated in various chronic inflammatory conditions, including age-related neurodegenerative diseases. The increase in chronic low-level inflammation seen with aging has also been linked to behavioral decline. Despite their acknowledged importance along the gut microbiota-immune-brain axis, there is limited evidence on how APCs change with aging. In this study, we examined age-related changes in myeloid APCs in the gut, spleen, and brain as well as changes in the gut microbiota and behavioral phenotype in mice ranging in age from 2 months up to 32 months of both sexes. Our data show that the number of peripherally-sourced myeloid APCs significantly increases with advanced aging in the brain. In addition, our data showed that age-related changes in APCs are subset-specific in the gut and sexually dimorphic in the spleen. Our work highlights the importance of studying myeloid APCs in an age-, tissue-, and sex-specific manner.

中文翻译:

外周来源的髓样抗原呈递细胞随着衰老的增加而增加

衰老与肠道微生物群-免疫-脑轴功能障碍有关,后者是大脑健康和中枢神经系统 (CNS) 疾病的主要调节轴。抗原呈递细胞 (APC) 在感知肠道微生物群的变化以及先天性和适应性免疫反应的调节方面发挥着重要作用。APC 还与各种慢性炎症有关,包括与年龄相关的神经退行性疾病。随着年龄的增长,慢性低水平炎症的增加也与行为下降有关。尽管它们在肠道微生物群 - 免疫 - 脑轴上的重要性得到公认,但关于 APC 如何随衰老变化的证据有限。在这项研究中,我们检查了肠道、脾脏、和大脑以及肠道微生物群和行为表型的变化,小鼠的年龄从 2 个月到 32 个月不等。我们的数据显示,外周来源的髓系 APC 的数量随着大脑的衰老而显着增加。此外,我们的数据显示,APC 的年龄相关变化在肠道中具有亚群特异性,在脾脏中具有性别二态性。我们的工作强调了以特定于年龄、组织和性别的方式研究髓系 APC 的重要性。
更新日期:2020-11-01
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