Critical role of IL-25 and its receptor in regulating eosinophilic inflammation in allergic asthma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

DU Wei ^1,2 , DU Juan ^1,2 , ZHOU Jun ^1,2 , SHI Guocao ^1,2 ,  TANG Wei ^1,2

1. Department of Respirology and Critical Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China;
2. Institute of Respiratory Diseases, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China;

Corresponding?author：

TANG Wei, Email: tina_tangwei@163.com

Keywords：

Asthma; Allergen challenge; Eosinophils; Interleukin-25; Interleukin-25 receptor

DOI：

10.7507/1671-6205.201805012

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Objective To investigate the role of interleukin-25 (IL-25) and its receptor during allergen challenge test in allergic asthmatics as well as its underlining mechanism.Methods Fifteen allergic asthmatic patients with dual response in allergen challenge test were enrolled and blood samples were collected before and after challenge test. The expression levels of IL-25 receptor on the surface of eosinophils, plasma and intracellular IL-25 levels were measured by flow cytometry and enzyme-linked immunosorbent assay. Besides, the function of eosinophils from these patients was evaluated through the expression of type 2 cytokines, degranulation and chemotaxis after stimulation with IL-25.Results Upon allergen challenge, the expression of IL-17RB on the surface of eosinophils were increased from (7 426±2 824)/10⁶ white blood cells to (19 446±5 593)/10⁶ white blood cells (P<0.001). The expression of IL-17RA/RB on eosinophils were significantly increased from (4 508±1 360)/10⁶ white blood cells to (9 025±3 166)/10⁶ white blood cells (P<0.001). The plasma level of IL-25 increased from (650±45) pg/ml to (851±43) pg/ml (7 hours after allergen challenge) and (813±56) pg/ml (24 hours after allergen challenge) (P<0.001). The intracellular IL-25 expression of eosinophils was also upregulated from (10 398±1 909)/10⁶ white blood cells to (147 684±46 222)/10⁶ white blood cells (P<0.05). In vitro study, IL-25 (1 ng/ml) stimulated eosinophils for 2 hours promoted its expression of peroxidase [(12.5±4.2) ng/ml compared to control (1.26±0.4) ng/ml, P<0.05). The intracellular expression of IL-5 and IL-13 in eosinophils were also increased after stimulated by IL-25. IL-25 (1 pg/ml) stimulation compared to control could increase eosinophil migration in eotaxin [(36±3) vs. (69±5), P<0.05).Conclusion IL-25 and its receptor play a critical role in eosinophilic aggregation, activation and mobilization during allergic inflammation in allergic asthmatics.

Citation： DU Wei, DU Juan, ZHOU Jun, SHI Guocao, TANG Wei. Critical role of IL-25 and its receptor in regulating eosinophilic inflammation in allergic asthma. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(3): 247-253. doi: 10.7507/1671-6205.201805012 Copy

1.	殷凱生. 氣道炎癥評估是支氣管哮喘控制評估的核心. 中華結核和呼吸雜志, 2015, 38(5): 324-326.
2.	張永明, 林江濤, 蘇楠, 等. 支氣管哮喘患者氣道炎癥表型研究. 中華結核和呼吸雜志, 2015, 38(5): 348-354.
3.	Yao X, Sun Y, Wang W, et al. Interleukin (IL)-25: Pleiotropic roles in asthma. Respirology, 2016, 21(4): 638-647.
4.	Lindén A, Dahlén B. Interleukin-17 cytokine signalling in patients with asthma. Eur Respir J, 2014, 44(5): 1319-1331.
5.	Yao X, Wang W, Li Y, et al. IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model. Respir Res, 2015, 16: 39.
6.	Yao XJ, Huang KW, Li Y, et al. Direct comparison of the dynamics of IL-25- and 'allergen'-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model. Clin Exp Allergy, 2014, 44(5): 765-777.
7.	Byers DE. Defining the roles of IL-33, thymic stromal lymphopoietin, and IL-25 in human asthma. Am J Respir Crit Care Med, 2014, 190(7): 715-716.
8.	Tang W, Smith SG, Beaudin S, et al. IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma. Int Arch Allergy Immunol, 2014, 163(1): 5-10.
9.	From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015. Available at: http://www.ginasthma.org.
10.	Cockcroft DW, Killian DN, Mellon JJ, et al. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy, 1977, 7(3): 235-243.
11.	Terrier B, Bieche I, Maisonobe T, et al. Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome. Blood, 2010, 116: 4523-4531.
12.	Smith SG, Imaoka H, Punia N, et al. The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils. PPAR Res, 2012, 2012: 235231.
13.	Cheung PF, Wong CK, Ip WK, et al. IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation. Allergy, 2006, 61(7): 878-885.
14.	Wong CK, Cheung PF, Ip WK, et al. Interleukin-25-induced chemokines and interleukin-6 release from eosinophils is mediated by p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB. Am J Respir Cell Mol Biol, 2005, 33(2): 186-194.
15.	Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol, 2009, 9(8): 556-567.
16.	Jung JS, Park BL, Cheong HS, et al. Association of IL-17RB gene polymorphism with asthma. Chest, 2009, 135(5): 1173-1180.
17.	Corrigan CJ, Wang W, Meng Q, et al. Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses. J Allergy Clin Immunol, 2011, 128(1): 116-124.
18.	Cheng D, Xue Z, Yi LL, et al. Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma. Am J Respir Crit Care Med, 2014, 190(6): 639-648.
19.	Lacy P, Rosenberg HF, Walsh GM. Eosinophil overview: structure, biological properties, and key functions. Methods Mol Biol, 2014, 1178: 1-12.
20.	Cockcroft DW, Davis BE, Boulet LP, et al. The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen. Allergy, 2005, 60(1): 56-59.
21.	Peebles RS Jr, Aronica MA. Proinflammatory pathways in the pathogenesis of asthma. Clin Chest Med, 2019, 40(1): 29-50.

1. 殷凱生. 氣道炎癥評估是支氣管哮喘控制評估的核心. 中華結核和呼吸雜志, 2015, 38(5): 324-326.
2. 張永明, 林江濤, 蘇楠, 等. 支氣管哮喘患者氣道炎癥表型研究. 中華結核和呼吸雜志, 2015, 38(5): 348-354.
3. Yao X, Sun Y, Wang W, et al. Interleukin (IL)-25: Pleiotropic roles in asthma. Respirology, 2016, 21(4): 638-647.
4. Lindén A, Dahlén B. Interleukin-17 cytokine signalling in patients with asthma. Eur Respir J, 2014, 44(5): 1319-1331.
5. Yao X, Wang W, Li Y, et al. IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model. Respir Res, 2015, 16: 39.
6. Yao XJ, Huang KW, Li Y, et al. Direct comparison of the dynamics of IL-25- and 'allergen'-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model. Clin Exp Allergy, 2014, 44(5): 765-777.
7. Byers DE. Defining the roles of IL-33, thymic stromal lymphopoietin, and IL-25 in human asthma. Am J Respir Crit Care Med, 2014, 190(7): 715-716.
8. Tang W, Smith SG, Beaudin S, et al. IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma. Int Arch Allergy Immunol, 2014, 163(1): 5-10.
9. From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015. Available at: http://www.ginasthma.org.
10. Cockcroft DW, Killian DN, Mellon JJ, et al. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy, 1977, 7(3): 235-243.
11. Terrier B, Bieche I, Maisonobe T, et al. Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome. Blood, 2010, 116: 4523-4531.
12. Smith SG, Imaoka H, Punia N, et al. The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils. PPAR Res, 2012, 2012: 235231.
13. Cheung PF, Wong CK, Ip WK, et al. IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation. Allergy, 2006, 61(7): 878-885.
14. Wong CK, Cheung PF, Ip WK, et al. Interleukin-25-induced chemokines and interleukin-6 release from eosinophils is mediated by p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB. Am J Respir Cell Mol Biol, 2005, 33(2): 186-194.
15. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol, 2009, 9(8): 556-567.
16. Jung JS, Park BL, Cheong HS, et al. Association of IL-17RB gene polymorphism with asthma. Chest, 2009, 135(5): 1173-1180.
17. Corrigan CJ, Wang W, Meng Q, et al. Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses. J Allergy Clin Immunol, 2011, 128(1): 116-124.
18. Cheng D, Xue Z, Yi LL, et al. Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma. Am J Respir Crit Care Med, 2014, 190(6): 639-648.
19. Lacy P, Rosenberg HF, Walsh GM. Eosinophil overview: structure, biological properties, and key functions. Methods Mol Biol, 2014, 1178: 1-12.
20. Cockcroft DW, Davis BE, Boulet LP, et al. The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen. Allergy, 2005, 60(1): 56-59.
21. Peebles RS Jr, Aronica MA. Proinflammatory pathways in the pathogenesis of asthma. Clin Chest Med, 2019, 40(1): 29-50.

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