University of Texas McGovern Medical School, Department of Neurology, Houston, TX, United States.
University of Connecticut School of Medicine, Farmington, CT, United States.
Brain Behav Immun. 2020 Nov;90:235-247. doi: 10.1016/j.bbi.2020.08.023. Epub 2020 Aug 27.
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.
衰老是与肠道微生物群-免疫-脑轴的功能障碍相关的，这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和调节先天和适应性免疫反应方面发挥着重要作用。APC 也与各种慢性炎症性疾病有关，包括与年龄相关的神经退行性疾病。随着衰老而出现的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-脑轴中具有公认的重要性，但关于 APC 如何随年龄变化的证据有限。在这项研究中，我们检查了从 2 个月到 32 个月大的雄性和雌性小鼠的肠道、脾脏和大脑中与年龄相关的髓样 APC 变化，以及肠道微生物群和行为表型的变化。我们的数据表明，随着大脑的衰老，外周来源的髓样 APC 的数量显著增加。此外，我们的数据表明，APC 的年龄相关变化在肠道中是亚群特异性的，在脾脏中是性别二态性的。我们的工作强调了以年龄、组织和性别特异性的方式研究髓样 APC 的重要性。
