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

Abstract

Human tissue-resident memory T (T_RM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of T_RM cells in the lung tissues of idiopathic pulmonary fibrosis patients. However, the functional consequences of T_RM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of T_RM cells, especially the CD8⁺ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8⁺ T_RM 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_RM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with chemokine CC-motif ligand (CCL18) induced CD8⁺ T_RM cell expansion and exacerbated fibrosis, whereas blocking C-C chemokine receptor 8 (CCR8) prevented CD8⁺ T_RM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8⁺ T_RM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8⁺ T_RM cells may be a potential therapeutic approach. NEW & NOTEWORTHY The role of CD8⁺ T_RM 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_RM cells, thereby exacerbating pulmonary fibrosis.

Keywords: CCL18; CCR8; CD8; pulmonary fibrosis; tissue-resident memory T cells.