CCR4/TARC Axis Recruits Regulatory T Cells And Th17Cells Into Lung Tissue Of Asthma In Mice

Objective To explore the regulation of CD4+CD25+Foxp3+Cell and Th17cell’s infiltration in the lung tissue via CCR4/TARC axis in mice model of asthmaMethods Twenty female BALB/C mice were assigned randomly to two groups by the according to random number table:a asthma group and a control group; 10 mice per group. The mice of asthma group were sensitized with ovalbumin(OVA) and repeatedly challenged with OVA, while the mice of control group were sensitized and challenged with equal PBS instead of OVA. After the last OVA challenge collected peripheral blood、serum and bronchoalveolar lavage fluid(BALF) of all the mice; disposed the left lung tissue with HE staining and performed pathological semi-quantitative score when observed the lung tissues inflammation via light microscope. Separated the lymphocytes from the right lung tissues. Both of the peripheral blood and the lymphocytes from the right lung tissues were used to test the changes of Treg cells and Thl7cells’percentages and also the expressions of CCR4 in treg cells and Th17 cells. Concentration of IL-17A and TARC in the serum and BALF were tested by enzyme linked immunosorbent assay.Results Pathologic changes in asthma mice lung tissue were bronchia mucosa incrassation, partial tear and nflammatory cells invasiveness around bronchia and blood vessel,while the same changes were not found in the control group. The percentage of CD4+CD25+ Foxp3+ cells subset was (4.54%± 2.65%) in the asthma group which was lower than the control group (11.54%± 1.80%), the difference was statistical significance(P<0.01). The percentage of CD4+IL-17+ cells subset was (2.58%±0.43%) in the asthma group which was higher than the control group (0.76%±0.15%) (p<0.01). The expression of CCR4 in the treg was 96.78%±1.18% in the asthma group and 96.50%± 2.07% in the control group, both were high, the difference was not statistical significance (p=0.76)。At the same time the high expression of CCR4 in the Th17 cells was showed which was 96.48%±1.72% in the asthma group and 96.18%±2.52% in the control group(p=0.77).And in each group the expression during Treg and Th17 cells was not statistical significance. The results of ELISA showed us that the concentration of IL-17A was very low both in serum and BALF which were collected from the two groups and difference was not statistical significance. For the TARC, the concentration in the serum was low in the two groups and either not statistical significance; whereas in the BALF the concentration of TARC was 108.27±62.16 pg/ml(asthma group)、41.07±18.95 pg/ml(control group) and the difference was statistical significance(p<0.01). The concentration of TARC in the BALF was positively correlated both with the pathological score of lung tissues inflammation(r=0.773,p< 0.05) and the percentage of Th17 cells in lung tissue(r=0.786, p=0.002).Conclusion The ratio of Foxp3+Treg/Th17 cell was declining in the murine model of asthma;The CCR4/TARC axis might be involved in regulating the infiltration of Th17 cells in the lung tissue in mice model of asthma.