Metabolic damage and premature thymus aging caused by stromal catalase deficiency (LYM2P.722)

• DOI: 10.4049/jimmunol.194.supp.62.3
• Publication Date: 2023-01-01T10:40:35Z
• Authors: Ann Griffith; Thomas Venables; Jianjun Shi; Andrew Farr; Holly Van Remmen; Luke Szweda; Mohammad Fallahi; Peter Rabinovitch; Howard Petrie
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Abstract T lymphocytes are essential mediators of immunity produced by the thymus in proportion to mass. The thymus atrophies rapidly with age, resulting in diminished new T cell production. Decreased thymic output is compensated by duplication of existing cells, but results in progressive dominance by memory T cells, and decreased ability to respond to new pathogens or vaccines. We find that accelerated thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by reactive oxygen species (ROS) generated during aerobic metabolism. Genetic complementation of catalase diminished atrophy, as did chemical antioxidants, providing a mechanistic link between antioxidants, metabolism, and normal immune function. Progenitor lymphoblasts represent the primary source of thymic ROS, likely acting on stromal cells in trans. We propose that thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely metabolic lymphoid environment.