The chronic inflammatory state associated with advanced age, known as inflammaging, is a well-described epidemiological risk factor for many common diseases of older people. However, less is known about the determinants of this phenotype, including whether the age-associated changes in immune function within tissues are associated with the ageing of tissue structural cells that form supportive niches. Allen et al. describe a structural basis for inflammaging in the lung by showing that aged tissue fibroblasts support the emergence of pro-inflammatory, granzyme K (GZMK)+ CD8+ T cells.
Using mice that the authors generated to track Gzmk expression, GZMK+ CD8+ T cells co-expressing PD1 were shown to emerge in BALT with ageing. Isolated GZMK+ cells did not proliferate in response to T cell receptor (TCR) stimulation but had increased interferon-γ (IFNγ) secretion compared with GZMK– cells, which suggests that this ageing-associated T cell population has mixed features of exhaustion and effector function.