[Mechanisms and dynamics of Th17 cells in mice with cigarette smoke-induced emphysema].

OBJECTIVE: To evaluate the expression of Th17 cell in a cigarette smoke-induced mice model of emphysema and explore the probable mechanisms of its elevation.
METHODS: Forty male Balb/c mice were randomly divided into 4 groups: control group for 12 weeks (C12), control group for 24 weeks (C24), smoke-exposure group for 12 weeks (S12) and smoke-exposure group for 24 weeks (S24)(n = 10 each). Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The percentages of Th17, Th1, Th17/Th1, CD4(+)IL-17(+)CCR6(+)T and CCR6(+)Th17 cells were determined by tetra-color flow cytometry while the levels of interleukin (IL)-1β, IL-6, IL-23, transforming growth factor (TGF)-β, interferon (IFN)-γ and CC chemokine ligand (CCL)-20 assayed by enzyme-linked immunosorbent assay (ELISA).
RESULTS: The values of Lm [(39 ± 4) µm, (47 ± 7) µm] and DI [(39.1 ± 1.6), (45.2 ± 3.1)] were significantly higher in S12 and S24 than those in C12 [(33 ± 3) µm, (28.2 ± 1.6)] and C24 [(32 ± 4) µm, (28.9 ± 2.1)], particularly in C24 (all P < 0.05). The percentages of Th17 cell [(3.27 ± 1.12), (7.19 ± 2.24)], Th17/Th1 cell [(0.61 ± 0.30), (1.82 ± 0.52)] and Th1 cell [(10.02 ± 3.68), (26.21 ± 6.04)] in the lungs of S12 and S24 significantly increased than those in C12 [(1.80 ± 0.75), (0.27 ± 0.12), (3.75 ± 1.72)] and C24 [(1.99 ± 0.59), (0.28 ± 0.11), (4.16 ± 1.32)], particularly in C24 (all P < 0.01). The percentages of Th17, Th17/Th1 and Th1 cells in the lungs of S12 and S24 had a positive correlation with Lm and DI (all P < 0.01). The percentages of CD4(+)IL-17(+)CCR-6(+)T cell [(0.69 ± 0.34), (1.11 ± 0.48)] and CCR6(+)Th17 cell [(12.23 ± 2.13), (18.65 ± 1.17)] were significantly elevated in S12 and S24 compared to those in C12 [(0.22 ± 0.18), (6.55 ± 2.13)] and C24 [(0.25 ± 0.17), (7.29 ± 1.57)], particularly in C24 (all P < 0.05). Furthermore, a positive correlation between CCR6(+)Th17 cell and emphysematous lesions was also found (all P < 0.05). The levels of IL-1β, IL-6, IL-23, TGF-β, IFN-γ and CCL20 significantly increased in S12 and S24 as compared with those of C12 and C24 (all P < 0.05). Meanwhile, the percentage of Th17 cell had a positive correlation with IL-1β, IL-6, IL-23, TGF-β, IFN-γ and CCL20.
CONCLUSION: There is an up-regulated expression of Th17 in lungs of cigarette smoke-induced emphysema mice. The CCR6/CCL20 axis and the elevated levels of IL-1β, IL-6, IL-23, TGF-β and IFN-γ may be related with the above effect.