Study Of CD4~+CD25~+T Regulatory Cells And Related Cytokines In The Experimental Mice With Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder. Continued fibrosis leads to loss of lung function and ultimately death, Numerous factors have been implicated in this process, the molecular mechanisms of IPF are still controversial and elusive, but there are some signs show that fibroblast, proliferation, extracellular matrix deposition, and progressive lung scarring are hallmarks of IPF, which result in inappropriate and dysregulated tissue remodeling and enhanced vascular remodeling. Conventional immunosuppressive therapy has yielded poor results. So, there maybe some other causes of IPF。Nowadays we have focus on the CD4+CD25+T regulatory cells, from which we made great progress on the pathogenesis and therapy of IPF. This study attempted to establish experimental BLM induced pulmonary fibrosis mouse model, by focus our attention on monitoring the changes of T regulate cells subsets in T-lymphocyte, we want to understand whether Treg cells and it's related cytokine play an important role in pulmonary fibrosis.After we establish experimental BLM induced pulmonary fibrosis mouse model, the alteration of Treg cells subpopulation in peripheral blood mononuclear cells(PBMS) and broncholveolar lavage(BAL) were analyzed, besides the level of cytokine of broncholveolar lavage was analyzed. The main results are as following:1. The levels of T lymphocyte subsets in peripheral blood in BLM group were significant higher than those in in control groups or normal saline groups at 2nd, 4th,8th,16th day. The levels of T lymphocyte subsets in broncholveolar lavage in BLM group were significant higher than those in in control groups or normal saline groups at 8th day. There is no significant difference between 3 groups in other days.2. The ratio of CD25+Foxp3+ T cells in the CD4+T cells of peripheral blood were significant lower than those in control groups or normal saline groups at 4th day. There is no significant difference between 3 groups in other days. The ratio of CD25+Foxp3+ T cells in the CD4+ T cells of broncholveolar lavage in BLM group were always significant lower than those in control groups or normal saline groups. 3. The cell concentration of Treg subsets of peripheral blood was significant lower than control groups at 2nd and 4th day, but at 8th day and 16th day it is significant higher than control groups, then reduced to normally level. The cell concentration of Treg subsets of broncholveolar lavage was significant higher than those in in control groups or normal saline groups at 4th,8th and 16th day than control groups.4. Level of IL-21, TGF-β,IL-1α, IL-1β, IL-2, IL-4, IL-6 and IFN-y in BAL was detected, results are as following:Level of IL-21 of BLM groups was significant lower than control groups at 2nd day,16th day and 32nd day; There is no significant difference between 3 groups in the level of TGF-β. Level of IL-la was significant lower than control groups at 2nd day,8th day,16th day and 32nd day; There is no significant difference between 3 groups in the level of IL-1β; Level of IL-2 of BLM groups was significant lower than control groups at 2nd day,8th day and 16th day; Level of IL-4 of BLM groups was significant lower than control groups at 16th day; Level of IL-6 of BLM groups was significant higher than control groups at 2nd day,4th day,8th day and 16th day, There is no significant difference between other groups; Level of IFN-y was significant lower than control groups at 2nd day,4th day,8th day and 16th day.Conclusion:This study showed that the reduction of Treg's rate in CD4+T cells play a significant role in the process of pulmonary fibrosis.