The role of endogenous "non-self" elements in the chronic inflammation and aging 内在的「非自己」の慢性炎症および老化における役割

Homeostasis of the living organism is endangered by the constant threat of exogenous pathogens, but also is by the endogenous “non-self” elements. Previous studies have unmasked the critical roles of the “non-self” elements such as endogenous retroelements (EREs) and latent herpes viruses in the pathogenesis of autoimmune diseases and neurodegeneration, as well as in the aging processes. EREs were originally exogenous retroviruses or retrotransposons that have been inserted into the host germline throughout the evolution, and whose suppression is critical in the maintenance of the host stability. With a CRISPR-based technique, we developed a system in which EREs are specifically targeted, and demonstrated the causal role of these elements in the pathogenic processes related to aging. Aside from this, in the chronic inflammation of post-acute sequelae of COVID-19 (or “Long COVID”), we found that reactivation of the latent herpes viruses could be playing key pathogenic roles. In this seminar, I will discuss the roles of these “non-self” elements, citing autoimmune diseases, neurodegeneration, and Long COVID as the examples.