| CHAPTER IFoxp3+regulatory T cell in lung tissues of smokers with normal lung function and patients with chronic obstructive pulmonary diseaseObjective:This study aimed to observe the expression of Foxp3+regulatory T cell (Treg cell) in the lung tissues of smokers with normal lung function and patients with COPD, and dicusse the role of Foxp3+Treg cell in the lung inflammation and acquired immune response.Methods:The patients with peripheral lung cancer who performed surgery were divided into non-somking group with normal lung function (N group,10cases), smoking group with normal lung function (S group,10cases) and smoking with stable COPD group (COPD group,10cases). The fresh normal lung tissues from the surgical specimens were selected, which is over5cm from the lung cancer resection. The average alveolar area was detected by HE, Foxp3+cells in alveolar walls were analysed by immunohistochemistry. The level of Foxp3mRNA in lung tissues was analyzed by quantitative real-time polymerase chain reaction (PCR). The levels of Foxp3protein in lung tissues was analyzed by Western blot.Results:The average alveolar area in COPD group(152345±24497μm2) was significantly larger than that in the S group (106551±15815μm2) and in N group (50708±14125μm2)(P<0.05). The CD4+T cells in alveolar wall in the COPD group (22±8/mm) were more than that in S group (16±6/mm) and in N group (6±2/mm). Foxp3+Treg cells in the COPD group (3±1/mm) were less than that in S group (4±1/mm) and N group (5±1/mm), and that in S group was less than in N group. The Foxp3mRNA expression in lung tissues was decreased in the COPD group (0.431±0.109) followed by that in S group (0.930±0.413), compared with that in N group (1.391±0.312)(P values were all<0.05). The Foxp3protein expression in lung tusses was decreased in COPD group (0.307±0.051) followed by that in S group (0.504±0.218), compared with that in N group (0.824±0.180)(P values<0.05). There was a negative correlation between the numbers of Foxp3+cells and CD4+cells (R=-0.681, P<0.001). And the Foxp3+cell number was negatively correlated with mean alveolar area (R=-0.797, P<0.001). The levels of Foxp3mRNA and protein in lung tissues were both positively correlated with FEV1%pred (R=0.601, P <0.001; R=0.573, P=0.001).Conclusions:The expression of Foxp3+T cell was decreased in the lung tissues of smokers with normal lung function and COPD patients, which was correlated with alveolar mean area and reduced lung function, suggesting decreased Foxp3+T cell may participate lung inflammation and acquired immune response in COPD patients. CHAPTER IITranscription factor Foxp3of regulatory T cell in the peripheral blood of chronic obstructive pulmonary disease patients at different stagesObjective:This study aim to observe the expression of transcription factor Foxp3of regulatory T cell (Treg cell) in the peripheral blood of somkers with normal lung function and patients with chronic obstructive pulmonary disease (COPD) at differernt stages.Methods:Subjects received treatment or physical examination in our hospital were selected and devided into non-somking group with normal lung function (N group,20cases), smoking group with normal lung function (S group,20cases), smoking with COPD in the Global initiative for Chronic Obstructive Lung Disease (GOLD)1and2(COPD1-2group,20cases) and smoking with COPD in GOLD3and4(COPD3-4group,20cases). The Foxp3mRNA expression in peripheral blood was analysed by quantitative real-time polymerase chain reaction (PCR).Results:The Foxp3mRNA levels in peripheral blood were decreased in COPD3-4group (0.498±0.235)and COPD1-2group (0.931±0.237) followed by that in S group (1.215±0.258), compared with that in N group (1.452±0.254)(P values were all<0.05). The expression of Foxp3mRNA was positively correlated with FEV1%pred (R=0.758, P<0.001).Conclusion:The expressions of Foxp3mRNA in smokers with normal lung function and COPD patients were decreased, especially in COPD patients at3-4stages, suggesting the decrease of Foxp3+Treg cell is invovled in the severity of COPD and the activation of acquired immune response in COPD patients. CHAPTER IIISingle nucleotide polymorphisms of Transcription Factor Foxp3in regulatory T cell and chronic obstructive pulmonatory diseaseObsjective:To investigate the single nucleotide polymorphisms (SNPs) of transcription factor Foxp3of regulatory T cell (Treg cell) in patients with chronic obstructive pulmonatory disease (COPD) at different stages, and discusse the risk factors of the SNPs.Methods:Subjects received treatment or physical examination in our hospital were selected and devided into non-somking group with normal lung function (N group,61cases), smoking group with normal lung function (S group,81cases), smoking with COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD)1and2(COPD1-2group,65cases) and smoking with COPD in GOLD3and4(COPD3-4group,117cases). Samples of peripheral blood were collected. The Foxp3SNPs rs2280883, rs3761548, rs3761549and rs5902434were analyzed by Tanman quantitative real-time polymerase chain reaction (PCR). The susceptibility of COPD in people with differernt genotypes, and the risk factors for genetic mutations were both analyzed by logistic regression model.Results:All four SNPs comply with Hardy-Weinberg genetic equilibrium. The genotypes and haplotypes of Foxp3SNP rs5902434were differently expressed in COPD3-4group, COPD1-2group, S group and N group (P<0.05). The-/-genotype was protective for COPD patients both at stage1-2and at stage3-4(COPD1-2group:OR=0.278,95%CI=0.079-0.974,; COPD3-4group:OR=0.235,95%CI=0.074-0.747). The genotype-/-of rs5902434was protective for patients with FEV1%pred=30-50(OR=0.222, 95%CI=0.094-0.525), as well as patients with FEV1/FVC<50and FEV1/FVC=50-70(FEV1/FVC<50:OR=0.295,95%CI=0.130-0.666; FEV1/FVC=50-70:OR=0.337,95%CI=0.131-0.866). The genotype-/ATT of rs5902434also could be protective for patients with FEV1%pred=30-50(OR=0.359,95%CI=0.150-0.863). The analysis of rs5902434haplotypes showed that-haplotype was susceptible to smokers with normal lung function (OR=1.746,95%CI=1.048-2.914). Furthermore,-haplotype was found to be protective for patients with FEV1%pred=30-50and FEV1/FVC<50, respectively (FEV1%pred=30-50:OR=0.582,95%CI=0.358-0.946; FEV1/FVC<50:OR=0.622,95%CI=0.403-0.961). The comprehensive analysis with smoking history, age, BMI and nation showed that non-Han people are more likely to have-/ATT genotype than Han people (OR=2.277,95%CI=1.022-5.072).Conclusions:The Foxp3SNP rs5902434was risk for COPD in males, and-/-genotype was protective for COPD and the decline of lung function. But smoking history and age didn’t influence this SNP. These foundings suggested that SNPs may be a up-stream factor of COPD. But risk factors of COPD including smoking and age maynot be associated with this SNP of Foxp3. |
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