Reversing thymus involution by targeting long-lived stem cells

随着年龄的增长，影响生活质量的疾病的发生率也会增加。这是一个多因素的过程，其特征是组织修复能力的进行性丧失，炎症、感染和癌症、退行性疾病和慢性疾病的发生率增加。有必要针对这样一个社会重大挑战，即60岁以上人口急剧增加，到2050年将翻一番，对卫生系统产生巨大影响。由于免疫系统内在的系统性，相互连接我们身体的所有器官，渐进性免疫衰老在这些与年龄相关的疾病中起着主要作用。胸腺是一个主要的淋巴器官，提供对病原体、癌症的免疫力，并建立长期的免疫记忆。然而，胸腺随着青春期开始退化，并持续到成年期，老年人基本上是萎缩的。衰老的胸腺降低了对疫苗接种的反应能力和消除自我反应免疫细胞的能力，从而导致炎症、自身免疫和癌症的发生。因此，迫切需要建立一种新的方法来开发能够逆转胸腺萎缩的治疗方法。逆转胸腺退化将增加循环中的抗炎免疫细胞，这一过程被称为免疫复兴。逆转百里香项目的主要目标是开发一个强大的筛选平台，以鉴定能够激活长期存活的、特征良好的人类上皮干细胞的新化合物，以恢复衰老或受损胸腺的胸腺基质功能和T细胞输出。宿主实验室开发的技术诀窍以及我们从衰老和患病胸腺中研究胸腺上皮细胞的能力决定了我们的竞争优势，即开发一种变革性的方法，在影响胸腺一生和衰老的几种条件下增强胸腺的功能。

Ageing is accompanied by increased incidence of disorders that impair quality of life. It is a multifactorial process characterized by a progressive loss of tissue repairing capacity with increased inflammation, infections, and incidence of cancer, degenerative andchronic disorders. There is a need to target a societal major challenge which is represented by the dramatic increased of people aged over 60 years that will double by 2050 with enormous impact on health systems. Due to the intrinsic systemic nature of the immune system interconnecting all organs in our body, progressive immune senescence plays a major role in these age-associated disorders.The thymus is a primary lymphoid organ that provides immunity against pathogens, cancer and establishes long-term immune memory. Nevertheless, the thymus starts involuting with puberty and continue into adulthood with essentially atrophy in the elderly. Aged thymus has reduced capacity to raise response to vaccination and ability to eliminate self-reacting immune cells, contributing to inflammation, autoimmunity and cancer occurrence. Therefore, there is an urgent need to build a novel approach for development of therapeutics able to reverse thymus atrophy. Reversing thymus involution will increase circulating anti-inflammatory immune cells, process known as immune rejuvenation.The REVERSE THYME project has the main goal to develop a robust screening platform for identification of novel compounds able to activate long-lived, well characterized human epithelial stem cells to restore thymic stroma function and T cell output in aged or damaged thymus. The know-how developed in the host laboratory and our capacity to study thymic epithelial cells from aged and diseased thymi define our competitive advantage to develop a transformative approach to enhance the function of the thymus in several conditions affecting it throughout life and ageing.