Fibroblast orchestration of inflammaging via NF-kB activation.

ABSTRACT: Aged tissue is characterized by chronic inflammation known as "inflammaging". While this aging immune phenotype supposedly drives some of the most common diseases affecting the elderly, little is known about the structural drivers of inflammaging. In this study, we demonstrate that age-dependent activation of NF-kB in tissue fibroblasts remodels the immune architecture, promoting the emergence of an exhausted T cell population (GZMK⁺/CD8⁺) recently identified in normal aging, as well as autoimmunity and cancer. Fibroblast-specific NF-kB activation triggered a fibroblast-macrophage-T cell circuit to form tertiary lymphoid structures in the lung and promoted the emergence of exhausted GZMK⁺ T cells. Fibroblastic activation of NF-kB increased host susceptibili

SUBMITTER: Allen NC 

PROVIDER: S-EPMC12622043 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature