The Change And Significance Of Th17 And Treg Related Cytokines In The Lung Tissue Of Mice With COPD That Dealt With Dendritic Cells Overexpressing SOCS1

Objective:To explore the possible role and significance of dendritic cells overexpressing suppressor of cytokine signaling-1(DC-SOCS1)in the pathogenesis of chronic obstructive pulmonary disease(COPD)through related cytokines pathways of Th17/Treg.Methods:In order to get immature dendritic cells(imDCs),DCs precursors were extracted from the femur and tibia of mice and stimulated by IL-4 and GM-CSF.The lentivirus overexpressing SOCS1 was constructed to infect the bone marrow-derived immature dendritic cells(imDCs)and gained target cells namely DC-SOCS1.Western blot was used to detect the expression of SOCS1 on DC-SOCS1.DC-SOCS1(1×10~6),DC-SOCS1(2×10~6),and imDCs(1×10~6)were adoptively immunized into the mice through the tail vein on the first and seventh day of smoke exposure,and mice injected with saline were used as control.On the 28th day of smoke exposure,all mice were sacrificed.Changes of Th17 related cytokines IL-17 and IL-23 and Treg related cytokines IL-10 and TGF-beta in lung tissue were detected by ELISA.Results:1.Bone marrow-derived dendritic cells of mice were successfully extracted,cultured and identified;2.The DC-SOCS1 was constructed successfully;3.The results of IL-17 and IL-23 in lung tissue of mice with COPD;(1)TransfusingdifferentDCs(imDCsandDC-SOCS1withdifferent concentrations)reduced the expression of IL-17 and IL-23,which was statistically significant(P<0.05)in mice with COPD.The levels of IL-17 and IL-23 were decreased in higher concentrations of DC-SOCS1(2×10~6)compared with the group of DC-SOCS1(1×10~6),which was statistically significant(P<0.05).(2)The levels of IL-17 and IL-23 in the groups injected on the first day were lower than the groups injected on the seventh day,which was statistically significant(P<0.05).(3)The first day transfusion of DC-SOCS1(2 x 10~6)produced the lowest IL-17 and IL-23.4.The results of IL-10 and TGF-βin lung tissue of mice with COPD;(1)Transfusing different DCs(imDCs and DC-SOCS1 with different concentrations)increased the expression of IL-10 and TGF-βin lung tissue of mice with COPD,which was statistically significant(P<0.05).The levels of IL-10 and TGF-βwere increasd in higher concentrations of DC-SOCS1(2×10~6)compared with the group of DC-SOCS1(1×10~6),which was statistically significant(P<0.05).(2)The levels of IL-10 and TGF-βin the groups injected on the first day were higher than the groups injected on the seventh day,which was statistically significant(P<0.05).Conclusions:(1)The intervention of imDCs and different concentrations of DC-SOCS1in mice with COPD at different time could reduce the expression of Th17 related pro-inflammatory cytokines IL-17 and IL-23 in lung tissues.Moreover,the higher concentration of DC-SOCS1 in earlier stage might reduce the inflammation in COPD and played an important role in the treatment of COPD.(2)The intervention of imDCs and different concentrations of DC-SOCS1 in mice with COPD at different time could increase the expression of Treg related anti-inflammatory and inhibitory cytokines IL-10 and TGF-βin lung tissues.And the higher concentration of DC-SOCS1 in earlier stage might enhance the anti-inflammatory effect or immune tolerance of COPD and played an important role in the prophylaxis and treatment of COPD.