Rejuvenation of mucosal immunosenescence by adipose tissue-derived mesenchymal stem cells
Rejuvenation of mucosal immunosenescence by adipose tissue-derived mesenchymal stem cells
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DOI：
10.1093/intimm/dxx001
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发表时间：
2017
影响因子：
4.4
通讯作者：
Akitoshi Tsuruhara;K. Aso;D. Tokuhara;J. Ohori;Masaki Kawabata;Y. Kurono;J. Mcghee;K. Fujihashi
中科院分区：
文献类型：
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作者：
Akitoshi Tsuruhara;K. Aso;D. Tokuhara;J. Ohori;Masaki Kawabata;Y. Kurono;J. Mcghee;K. Fujihashi
粘膜免疫系统中与年龄相关的改变通常被称为粘膜免疫衰老。老化粘膜的主要变化是无法引发抗原特异性分泌型 IgA (SIgA) 抗体反应，而这种反应是宿主防御粘膜表面各种病原体的关键因素。在这方面，补偿老年人的粘膜失调以保持老年健康将是首要任务。我们已成功在老年（2 岁）小鼠中建立了抗原特异性 SIgA 抗体反应，通过使用由编码 Flt3 配体 (pFL) 的质粒和 CpG ODN 组成的新佐剂系统，提供对肺炎链球菌和流感病毒感染的保护性免疫力。为了探索当前粘膜疫苗策略对老年人的可能用途，我们在粘膜疫苗接种之前将脂肪组织来源的间充质干细胞（AMSC）过继转移到老年小鼠体内。这种免疫疗法成功地在老年小鼠的肠粘膜中产生了保护性抗原特异性抗体反应，其反应与年轻成年小鼠的反应相当。在这方面，我们假设过继转移的 AMSCs 可以增强老年小鼠的树突状细胞功能。这篇简短的综述讨论了 AMSC 在免疫衰老中恢复粘膜免疫的潜在细胞和分子机制。干细胞转移系统可能是逆转粘膜免疫衰老的一种有吸引力且有效的免疫干预策略。
Age-associated alterations in the mucosal immune system are generally termed mucosal immunosenescence. The major change seen in the aged mucosa is a failure to elicit an antigen-specific secretory IgA (SIgA) antibody response, which is a central player for host defense from various pathogens at mucosal surfaces. In this regard, it would be a first priority to compensate for mucosal dysregulation in the elderly in order to maintain their health in aging. We have successfully established antigen-specific SIgA antibody responses in aged (2 years old) mice, which provide protective immunity from Streptococcus pneumoniae and influenza virus infections, by using a new adjuvant system consisting of a plasmid encoding Flt3 ligand (pFL) and CpG ODN. In order to explore possible use of current mucosal vaccine strategies for the elderly, we have adoptively transferred adipose tissue-derived mesenchymal stem cells (AMSCs) to aged mice prior to mucosal vaccination. This immune therapy successfully resulted in protective antigen-specific antibody responses in the intestinal mucosa of aged mice that were comparable to those seen in young adult mice. In this regard, we postulate that adoptively transferred AMSCs could augment dendritic cell functions in aged mice. The potential cellular and molecular mechanisms whereby AMSCs restore mucosal immunity in immunosenescence are discussed in this short review. A stem cell transfer system could be an attractive and effective immunologic intervention strategy to reverse mucosal immunosenescence.