IL-17A inhibits Th2 cell differentiation and alleviates eosinophilic airway inflammation in a mouse model of asthma-

Yijie Wang; Shengtao Zhao; Xu Yang; Ran Wang; Donglin Guo; Yunqiu Jiang; Changzheng Wang

doi:10.16016/j.1000-5404.201612143

您当前的位置：

首页 >

文章列表页 >

IL-17A inhibits Th2 cell differentiation and alleviates eosinophilic airway inflammation in a mouse model of asthma-

更新时间：2026-02-09

- IL-17A inhibits Th2 cell differentiation and alleviates eosinophilic airway inflammation in a mouse model of asthma-
- Journal of Third Military Medical University Vol. 39, Issue 10, Pages: 954-959(2017)
- 作者机构：
  
  400037 重庆，第三军医大学新桥医院全军呼吸内科研究所，全军呼吸病研究重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81270075)
- DOI：10.16016/j.1000-5404.201612143
  CLC： R392.11;R392.3;R562.25
- Received：20 December 2016，
  
  Revised：2017-01-30，
  
  Published：30 May 2017
- 稿件说明：
移动端阅览
Yijie Wang, Shengtao Zhao, Xu Yang, et al. IL-17A inhibits Th2 cell differentiation and alleviates eosinophilic airway inflammation in a mouse model of asthma-[J]. Journal of Third Military Medical University, 2017, 39(10): 954-959.
DOI：

Yijie Wang, Shengtao Zhao, Xu Yang, et al. IL-17A inhibits Th2 cell differentiation and alleviates eosinophilic airway inflammation in a mouse model of asthma-[J]. Journal of Third Military Medical University, 2017, 39(10): 954-959. DOI： 10.16016/j.1000-5404.201612143.

摘要

目的

研究IL-17A对哮喘小鼠Th2细胞分化及其相关炎症的作用。

方法

24只C57BL/6J小鼠按随机数字表法分为对照组、哮喘组和IL-17A处理组（

＝ 8）。哮喘组和IL-17A处理组予以卵清蛋白（ovalbumin，OVA）致敏及激发。每次雾化激发前1 h，IL-17A处理组给予重组小鼠IL-17A气道滴入。各步对照均予以生理盐水。末次激发后24 h处死小鼠，收集支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）行细胞总数及分类计数。ELISA检测BALF中IL-4、IL-5、IFN-γ、IL-17A的浓度。HE和PAS染色及半定量评分评估小鼠肺部病理变化。流式细胞术检测脾脏和支气管淋巴结Th细胞分化。免疫磁珠分选健康小鼠幼稚CD4

T细胞，用Th2极化培养基体外培养，并给予IL-17A或等量PBS干预，检测Th2细胞的增殖

、凋亡和分化。

结果

哮喘组较对照组，BALF中细胞总数、嗜酸性粒细胞数及其比例（

＜0.05）、IL-4、IL-5、IL-17A浓度均显著增高（

＜0.05），IFN-γ浓度显著下降（

＜0.05）；支气管、血管周围炎症细胞浸润和杯状细胞化生明显加重（

＜0.01）；脾脏和淋巴结Th2细胞分化比例显著增高（

＜0.05）。IL-17A处理组较哮喘组，BALF中的细胞总数[（26.00 ± 5.43）× 10

/mL

（58.40 ± 26.93）× 10

/mL，

＜0.05

]

、嗜酸性粒细胞数[（8.04 ± 1.98）× 10

/mL

（31.95 ± 12.28）× 10

/mL，

＜0.05

]

及其比例[（29.93 ± 3.03）%

（53.47 ± 6.62）%，

＜0.01

]

显著降低，而中性粒细胞数及其比例无明显变化；BALF中Th2相关因子IL-4浓度[（9.86 ±2.77）pg/mL

（28.13 ± 4.62）pg/mL，

＜0.01

]

、IL-5浓度[（7. 30 ± 0. 50）pg/mL

（10.50 ± 1.10）pg/mL，

＜0.01

]

均显著降低；支气管、血管周围炎症细胞浸润减轻，HE染色半定量评分降低[（2.00 ± 0.51）

（3.12 ± 0.64），

＜0.05

]

，杯状细胞化生减少[（0.80 ± 0.45）

（2.40 ± 0.55），

＜0.01

]

；脾脏[（2.24 ± 0.44）%

（4.82 ± 1.83）%，

＜0.01

]

和淋巴结[（7.05 ± 0.58）%

（10.57 ± 1.35）%，

＜0.05

]

中Th2细胞分化比例显著减少。极化培养的幼稚CD4

T细胞，予IL-17A干预后，诱导分化的Th2细胞比例显著减少（

＜0.05），而增殖和凋亡无显著变化。

结论

IL-17A有抑制Th2细胞分化，减轻哮喘小鼠气道嗜酸性粒细胞炎症的作用。

Abstract

Objective

To investigate the effect of IL-17A on the differentiation of Th2 cells and airway inflammation in a mouse model of asthma.

Methods

Twenty-four C57BL/6J mice were randomly divided into control group

asthmatic group and IL-17A treatment group. The mice in asthmatic group and IL-17A treatment group were sensitized and challenged with ovalbumin (OVA)

and in the latter group

the mice received intratracheal instillation of IL-17A 1 h before each OVA challenge; normal saline was used for all the control treatments. The mice were sacrificed 2

4 h after the last challenge

and the bronchoalveolar lavage fluid (BALF) were collected for cytological examination and detection of IL-4

IL-5

IL-17A

and interferon-γ(IFN-γ) using ELISA. The lung pathologies were assessed semi-quantitatively using HE and PAS staining. The differentiation of Th cells in the spleen and tracheobronchial lymph nodes were analyzed with flow cytometry. The effects of IL-17A on cell proliferation

apoptosis

and differentiation were examined in naive CD4

T cells sorted by immunomagnetic beads from normal mice.

Results

Compared with the control mice

the asthmatic mice showed significantly increased total cell and eosinophil counts and eosinophil percentage (

0.05)

elevated IL-4

IL-5

and IL-17A concentrations (

0.05)

and lowered IFN-γ concentration in the BALF (

0.05). The asthmatic mice presented with more obvious inflammatory cell infiltration (

0.01) and goblet cell hyperplasia (

0.05) and significantly increased proportion of Th2 cells in the spleen and lymph nodes (

0.05). IL-17A treatment of the asthmatic mice significantly reduced the total cell number [(26.00 ± 5.43) × 10

/mL

(58.40 ± 26.93) × 10

/mL

0.05

]

eosinophil count [(8.04 ± 1.98) × 10

/mL

(31.95 ± 12.28) × 10

/mL

0.05

]

and eosinophil percentage [(29. 93 ± 3. 03)%

(53.47 ± 6.62)%

0.01

]

in the BALF without affecting neutrophil count or percentage. IL-17A treatment also resulted in lowered levels of IL-4 (9.86 ± 2.77 pg/mL

28.13 ± 4.62 pg/mL

0.01) and IL-5 (7.30 ± 0.50 pg/mL

10.50 ± 1.10 pg/mL

0.01) in the BALF

alleviated inflammatory cell infiltration (2. 00 ± 0.51

3.12 ± 0.64

0.05) and goblet cell hyperplasia (0.80 ± 0.45

2. 40 ± 0.55

0.01)

and reduced the percentages of Th2 cells in the spleen [(2.24 ± 0.44)%

(4.82 ± 1.83)%

0.01

]

and lymph nodes [(7.05 ± 0.58)%

(10.57 ± 1.35)%

0.05

]

. In naive CD4

T cells from normal mice

IL-17A treatment obviously inhibited cell differentiation into Th2 cells in vitro [(4.15 ± 0.55)%

(2.53 ± 0.47)%

0.05

]

without affecting the cell proliferation or apoptosis.

Conclusion

IL-17A can inhibit the differentiation of Th2 cells and alleviate eosinophilic airway inflammation in mice.

关键词

Keywords

references

Afshar R, Medoff B D, Luster A D. Allergic asthma: a tale of many T cells[J]. Clin Exp Allergy, 2008, 38(12): 1847-1857. DOI: 10.1111/j.1365-2222.2008.03119.x.

Fahy J V. Type 2 inflammation in asthma--present in most, absent in many[J]. Nat Rev Immunol, 2015, 15(1): 57-65. DOI: 10.1038/nri3786.

Lindén A, Dahlén B. Interleukin-17 cytokine signalling in patients with asthma[J]. Eur Respir J, 2014, 44(5): 1319-1331. DOI: 10.1183/09031936.00002314.

Park S J, Lee Y C. Interleukin-17 regulation: an attractive therapeutic approach for asthma[J]. Respir Res, 2010, 11: 78. DOI: 10.1186/1465-9921-11-78.

Hellings P W, Kasran A, Liu Z, et al. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma[J]. Am J Respir Cell Mol Biol, 2003, 28(1): 42-50. DOI: 10.1165/rcmb.4832.

Kinyanjui M W, Shan J, Nakada E M, et al. Dose-dependent effects of IL-17 on IL-13-induced airway inflammatory responses and airway hyperresponsiveness[J]. J Immunol, 2013, 190(8): 3859-3868. DOI: 10.4049/jimmunol.1200506.

Zhao S, Jiang Y, Yang X, et al. Lipopolysaccharides promote a shift from Th2-derived airway eosinophilic inflammation to Th17-derived neutrophilic inflammation in an ovalbumin-sensitized murine asthma model[J]. J Asthma, 2016: 1-9. DOI: 10.1080/02770903.2016.1223687.

Lawrenz M B, Fodah R A, Gutierrez M G, et al. Intubation-mediated intratracheal (IMIT) instillation: a noninvasive, lung-specific delivery system[J]. J Vis Exp, 2014(93): e52261. DOI: 10.3791/52261.

Myou S, Leff A R, Myo S, et al. Blockade of Inflammation and Airway Hyperresponsiveness in Immune-sensitized Mice by Dominant-Negative Phosphoinositide 3-Kinase-TAT[J]. J Exp Med, 2003, 198(10): 1573-1582. DOI: 10.1084/jem.20030298.

Flaherty S, Reynolds J M. Mouse Naive CD4 + T Cell Isolation and In vitro Differentiation into T Cell Subsets[J ] . Journal of Visualized Experiments, 2015(98). DOI: 10.3791/52739.

Tian B P, Hua W, Xia L X, et al. Exogenous interleukin-17A inhibits eosinophil differentiation and alleviates allergic airway inflammation[J]. Am J Respir Cell Mol Biol, 2015, 52(4): 459-470. DOI: 10.1165/rcmb.2014-0097OC.

Murdoch J R, Lloyd C M. Resolution of allergic airway inflammation and airway hyperreactivity is mediated by IL-17-producing {gamma}{delta}T cells[J]. Am J Respir Crit Care Med, 2010, 182(4): 464-476. DOI: 10.1164/rccm.200911-1775OC.

Schnyder-Candrian S, Togbe D, Couillin I, et al. Interleukin-17 is a negative regulator of established allergic asthma[J]. J Exp Med, 2006, 203(12): 2715-2725. DOI: 10.1084/jem.20061401.

Gaffen SL. Structure and signalling in the IL-17 receptor family[J]. Nat Rev Immunol, 2009, 9(8): 556-567. DOI: 10. 1038/nri2586.

Yamane H, Zhu J, Paul W E. Independent roles for IL-2 and GATA-3 in stimulating naive CD4 + T cells to generate a Th2-inducing cytokine environ ment[J ] . J Exp Med, 2005, 202(6): 793-804. DOI: 10.1084/jem.20051304.

Zhu J, Yamane H, Paul W E. Differentiation of effector CD4 T cell populations (*)[J]. Annu Rev Immunol, 2010, 28: 445-489. DOI: 10.1146/annurev-immunol-030409-101212.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Establishment of mouse model of immune tolerance of asthma through subcutaneous injection of high dose of ovalbumin

Establishment of mouse model of asthma airway remodeling and investigation of pathological features

Alteration of circulating eosinophila microparticles in asthmatic patients before and after treatment

Effect of maternal 1α,25-dihydroxyvitamin D3 supplement on allergic airway inflammation of its offspring in mouse asthma model

Interaction of indoleamine 2, 3-dioxygenase and CD4⁺CD25⁺Foxp3⁺ regulatory T cell in asthmatic mice

Related Author

廖伟

吴雪婷

曾靖

范文婷

汪金玉

钟世民

胡琦

王彦

Related Institution

No data

⁰