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

Human tissue-resident memory T (T) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of T cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of T cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of T cells, especially the CD8 subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8 T cells in mouse lungs accordingly altered the severity of fibrosis. In addition, the adoptive transfer of CD8 T cells containing a large number of CD8 T cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8 T cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8 T recruitment and inhibited pulmonary fibrosis. In conclusion, CD8 T cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8 T cells may be a potential therapeutic approach. The role of CD8 T cells in the development of pulmonary fibrosis was validated and studied in the classic model of pulmonary fibrosis. It was proposed for the first time that CCL18 has a chemotactic effect on CD8 T cells, thereby exacerbating pulmonary fibrosis.