AUTHOR=Santiago-Cruz Wendolaine , Espinosa Enrique , Pérez-Lara Jocelyn C. , Romero-Ramírez Héctor , Devarajan Priyadharshini , García-García Fabio , Rodríguez-Alba Juan C. 
  
TITLE=CD38 promotes LPS-induced innate-like activation and proliferation of CD8+ T lymphocytes in aged mice
  
JOURNAL=Frontiers in Aging
  
VOLUME=Volume 6 - 2025
  
YEAR=2025
  
URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2025.1701685
  
DOI=10.3389/fragi.2025.1701685
  
ISSN=2673-6217
  
ABSTRACT=CD38 is a transmembrane glycoprotein involved in NAD+ metabolism, calcium signaling, and immune cell activation. Its role in the inflammatory response has been studied extensively in innate immune cells; however, its contribution to the activation of memory T lymphocytes under inflammatory conditions is less understood. Additionally, recent studies have shown an age-related increase in the expression of the protein CD38 in various human and murine tissues. Moreover, CD8+ bystander T cells have been shown to contribute to inflammation during the aging process. Given the importance of its potential role in age-related pathologies, we examined the effect of CD38 on bystander activation of CD8+ memory T cells in aged mice following lipopolysaccharide challenge. CD38-deficient mice exhibited attenuated serum cytokine responses (IL-1β, IL-6, IFN-γ, and IL-10) and a distinct CD8+ T cell profile, characterized by a decrease in activated T cells. Wild-type mice displayed a significant expansion of CD69+TCM cells after LPS inoculation, an effect that was absent in CD38-deficient animals. LPS also promoted the expression of CD69 and CD38 in TEM/EFF subsets. Thus, our findings reveal a CD38-dependent mechanism underlying bystander activation of memory CD8+ T cells in aging. Highlighting the potential contribution of CD38 to age-related diseases, such as autoimmunity, and in the face of inflammatory conditions in aged people.