Another study on emphysema mice demonstrated that cigarette smoke not only increased the percentage of IL-21+ Th17 and IL-21R+ CD8+ T cells in peripheral blood, but also enhanced their expressions of IL-17 and IL-21, which in turn upregulated perforin and granzyme B in CD8+ T cells, indicating that cytotoxic function of CD8 + T cells can be regulated by Th17 cells in emphysema [58]. This evidence concerns the gene PRF1 and pulmonary emphysema.