The Th17/Treg Imbalance in the Pathogenesis of Asthma in a Mouse Model_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHOU Chen ¹ , CHEN Junhao ² ,  YIN Kaisheng. ³

Department of Pulmonary Medicine, Gerontology Research Institution of Jiangsu Province. Nanjing, Jiangsu, 210024, ChinaCorresponding Author: YIN Kai-sheng, E-mail: yinks@ 126. com;

Corresponding author：

YIN Kaisheng., Email: yinks@126.com

Keywords：

Asthma; T helper 17 cells; Regulatory T cells; Interleukin-17; Interleukin-10

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Objective To investigate the role of T helper 17 ( Th17) cells and CD4 + CD25 + Foxp3+regulatory T cells ( Treg) in the pathogenesis of asthma in a mouse model. Methods Twenty-four BALB/ c mice were randomly divided into an asthma group and a normal control group, with 12 mice in each group.Asthma model was established by ovalbumin sensitization and aerosol challenge in the asthma group. Airway reactivity was measured by plethysmography. The total and differential cell counts in bronchoalveolar lavage fluid ( BALF) were measured. The ratio of Th17 and Treg cells to mononuclear cells in the spleens of mice were detected by flow cytometry. The levels of IL-17 and IL-10 in BALF and lung homogenates were measured by ELISA. Results The bronchial provocation test showed that the average lung resistance increased remarkably in the asthma group. In spleens of the asthmatic mice, the percentage of Th17 cells was significantly higher [ ( 5.68 ±1. 99)% vs ( 2.80 ±0. 82) %, P lt; 0. 01] , and the percentage of Treg cells was significantly lower [ (2.88 ±0. 46) % vs ( 6.10 ±2.44) % , P lt; 0. 01] , with the ratio of Th17 to Treg significantly increased( 1. 93 ±0. 41 vs 0. 50 ±0. 15,P lt;0. 01) . In BALF and lung homogenates of the asthma group, the level of IL-17 was significantly higher[ ( 22. 37 ±3. 00) pg/mL vs ( 11. 42 ±2. 15) pg/mL, ( 52. 93 ±5. 39) pg/mL vs ( 19. 38 ±2. 65) pg/mL, both P lt; 0. 01] , and the level of IL-10 was significantly lower[ ( 6. 05 ±1. 25) pg/mL vs ( 14. 23 ±
2. 94) pg/mL, ( 9. 33 ±1. 79) pg/mL vs ( 21. 40 ±2. 44) pg/mL, both P lt; 0. 01] compared with the control group.Conclusion The imbalance of Th17/ Treg plays an important role in the pathogenesis of asthma.

Citation： ZHOU Chen,CHEN Junhao,YIN Kaisheng.. The Th17/Treg Imbalance in the Pathogenesis of Asthma in a Mouse Model. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(1): 28-31. doi: Copy

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4.	陈军浩,吴超,欧阳建,等.CpG-ODN216刺激健康人外周血淋巴细胞THI/TH2细胞因子的表达.临床检验杂志,2007,25:192-193.
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6.	Semik-Orzech A,Barczyk A,Pierzcha?a W. The role of interleukin 17A in inducing neutrophilic inflammation in the pulmonary tract. Pol Merkur Lekarski,2007,22:163-168.
7.	Bullens DM,Truyen E,Coteur L,et al.IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res,2006,7:135-138.
8.	Mangan PR,Harrington LE,O’Quinn DB,et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature,2006,441:231-234.
9.	Korn T,Bettelli E,Gao W,et al.IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature,2007,448:484-487.
10.	O’Quinn DB,Palmer MT,Lee YK,et al.Emergence of the Th17 pathway and its role in host defense.Adv Immunol,2008,99:115-163.
11.	Yang XO,Pappu BP,Nurieva R.et al.T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity,2008,28:29-39.
12.	吴奎,孙鲲,毕玉田,等.哮喘小鼠CD4+CD25+ 调节性T细胞数量及功能的改变.中国呼吸与危重监护杂志.2005,4:455-458.

1. Park H,Li Z,Yang XO,et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 1.Nat Immunol,2005,6:1133-1141.
2. Harrington LE,Hatton RD,Mangan PR,et al.Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages.Nat Immunol,2005,6:1123-1132.
3. Nguyen KD,Fohner A,Booker JD,et al. XCL1 enhances regulatory activities of CD4+ CD25(high) CD127(low/-) T cells in human allergic asthma. J Immunol,2008,181:5386-5395.
4. 陈军浩,吴超,欧阳建,等.CpG-ODN216刺激健康人外周血淋巴细胞THI/TH2细胞因子的表达.临床检验杂志,2007,25:192-193.
5. Bettelli E,Carrier Y,Gao W,et al.Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature,2006,441:235-238.
6. Semik-Orzech A,Barczyk A,Pierzcha?a W. The role of interleukin 17A in inducing neutrophilic inflammation in the pulmonary tract. Pol Merkur Lekarski,2007,22:163-168.
7. Bullens DM,Truyen E,Coteur L,et al.IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res,2006,7:135-138.
8. Mangan PR,Harrington LE,O’Quinn DB,et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature,2006,441:231-234.
9. Korn T,Bettelli E,Gao W,et al.IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature,2007,448:484-487.
10. O’Quinn DB,Palmer MT,Lee YK,et al.Emergence of the Th17 pathway and its role in host defense.Adv Immunol,2008,99:115-163.
11. Yang XO,Pappu BP,Nurieva R.et al.T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity,2008,28:29-39.
12. 吴奎,孙鲲,毕玉田,等.哮喘小鼠CD4+CD25+ 调节性T细胞数量及功能的改变.中国呼吸与危重监护杂志.2005,4:455-458.

Chinese Journal of Respiratory and Critical Care Medicine

The Th17/Treg Imbalance in the Pathogenesis of Asthma in a Mouse Model

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