CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

PM2.5 exposure-induced senescence-associated secretory phenotype in airway smooth muscle cells contributes to airway remodeling.

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.