Immune gene expression dynamics across the lifespan of Tibetan macaques (<i>Macaca thibetana</i>)

Abstract The immune system is essential for environmental adaptation and health maintenance in mammals. However, the dynamics of immune gene expression in nonhuman primates throughout their lifespan remain poorly understood. In this study, we performed a comprehensive transcriptomic analysis using RNA sequencing technology on 16 Tibetan macaques (Macaca thibetana), comprising three infants, four adolescents, four adults, and five old individuals. We identified differentially expressed genes and determined age-associated changes in the immune system. A total of 13,376 age-related differentially expressed genes were identified; pairwise comparisons revealed increasing and then decreasing differentially expressed gene numbers between consecutive stages: 997 (infant vs. adolescent), 1,742 (adolescent vs. adult), and 1,380 (adult vs. old). The results of the enrichment analysis indicated a significant enrichment of genes related to immune responses in immature macaques, highlighting the critical roles of the identified differentially expressed genes in orchestrating immune responses. The sustained expression of FOXO3 in old individuals exhibiting immunosenescence suggests a potential role in maintaining immune balance, although its function in Tibetan macaques needs to be validated. Mfuzz clustering revealed complex nonlinear changes in immune responses at critical life stages, further elucidating the dynamics of immune alterations. Our comprehensive description of the life cycle immunodynamics of Tibetan macaques lays the foundation for further studies on immune enhancement and disease prevention in this species, provides an important resource for understanding age-related changes in primates, and promotes the development of primate immunology.