Export file:

Format

  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text

Content

  • Citation Only
  • Citation and Abstract

Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26

1 Unit Research 12SP15 “Homeostasis and Molecular Dysfunction in the lung” Abderrahman Mami Hospital, Pavillon B, Ariana, Tunisia
2 Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
3 Division of Paediatric Respiratory Diseases, Pavillon B, A. Mami Hospital, Ariana, Tunisia

Topical Section: Cytokine function

Background: Asthma is an immunological disorder in which T helper 2 (Th2)-type cells and inflammatory cytokines have a prominent role in its pathogenesis. B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. Objective: In the present study of asthmatic patients we measured the soluble isoforms of BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) in induced sputum fluid with the aim to evaluate their utility as responsible for exacerbation. Methods: Eighty patients with asthma and 30 healthy controls (HC) were included in the study. Sputum fluid concentrations of sBTLA, sCTLA-4 and sPD-1 were measured with ELISA. Comparisons were made with Mann-Whitney U test and correlations with IL-17, IL-26 levels and FEV1 (%) were assessed with Spearman’s Rank correlation test. Results: sBTLA levels were significantly higher in the severe and moderate asthmatic patients compared to healthy controls. Significant differences were observed between severe and moderate asthmatics (p < 0.0001). No significant differences were found between mild asthmatics and healthy controls (p = 0.799). Soluble PD-1 levels were higher in severe and moderate asthmatic patients compared to HC and no significant difference was observed between these two asthmatic groups (p = 0.124). Mild asthmatics and control subjects expressed similar sPD-1 levels (p = 0.856). Soluble CTLA-4 was exclusively expressed in certain severe asthmatic patients. IL-17 inflammatory cytokine was significantly correlated with BTLA and sPD-1. IL-17 and IL-26 cytokines were highly expressed in sputum asthmatic groups compared to sputum from HC. Severe asthmatic group was characterized by the highest levels of both IL-17 and IL-26 mediators. Soluble BTLA correlates positively with IL-17 (r = 0.817; p < 0.0001) and IL-26 (r = 0.805; p < 0.0001) inflammatory cytokines. IL-17 and IL-26 levels were associated with the asthma clinical severity from severe to mild asthma (p < 0.0001). The inflammatory cytokines IL-17 and IL-26 were positively correlated with the percentages of macrophages, PNN and FEV1 (%). Conclusion: Here, we provide the first report on the increased expression of sBTLA and sPD-1 in induced sputum of severe asthmatics. IL-26 and IL-17 appeared as a novel proinflammatory axis. Both sBTLA and sPD-1 might be involved in the pathogenesis of asthma and were associated with a poor prognosis.
  Figure/Table
  Supplementary
  Article Metrics

Keywords severe asthma; induced sputum; sBTLA; sCTLA4; sPD-1; IL-17; IL-26

Citation: Sabrine Louhaichi, Mariem Salhi, Anissa Berraïes, Besma Hamdi, Jamel Ammar, Kamel Hamzaoui, Agnès Hamzaoui. Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26. AIMS Allergy and Immunology, 2018, 2(1): 10-23. doi: 10.3934/Allergy.2018.1.10

References

  • 1. Cosmi L, Liotta F, Maggi L, et al. (2017) Role of Type 2 innate lymphoid cellsin allergic diseases. Curr Allergy Asthm R 17: 66–72.    
  • 2. Galowitz S, Chang C (2015) Immunobiology of critical pediatric asthma. Clin Rev Allerg Immu 48: 84–96.    
  • 3. Charrad R, Berraïes A, Hamdi B, et al. (2016) Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A. Immunobiology 221: 182–187.    
  • 4. Bernard A, Lamy AL, Alberti I (2002) The two-signal model of T-cell activation after 30 years. Transplantation 73: S31–S35.    
  • 5. Boulougouris G, Mcleod JD, Patel YI, et al. (1998) Positive and negative regulation of human T cell activation mediated by the CTLA-4/CD28 ligand CD80. J Immunol 161: 3919–3924.
  • 6. Freeman GJ, Long AJ, Iwai Y, et al. (2000) Engagement of the PD-1immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192: 1027–1034.    
  • 7. Wang XF, Chen YJ, Wang Q, et al. (2007) Distinct expression and inhibitory function of B and T lymphocyte attenuator on human T cells. HLA 69: 145–153.
  • 8. Waterhouse P, Penninger JM, Timms E, et al. (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270: 985–988.    
  • 9. Boomer JS, Jennifer SS, Hotchkiss RS, et al. (2012) A prospective analysis of lymphocyte phenotypeand function over the course of acute sepsis. Crit Care 16: R112.    
  • 10. Van WC, Bateman ED, Bousquet J, et al. (2008) Asthma management pocket reference 2008. Allergy 63: 997–1004.    
  • 11. Berraïes A, Hamdi B, Ammar J, et al. (2016) Increased Expression of Thymic Stromal Lymphopoietin in induced sputum from asthmatic children. Immunol Lett 178: 85–91.    
  • 12. Moermans C, Heinen V, Nguyen M, et al. (2011) Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease. Cytokine 56: 298–304.    
  • 13. Delvaux M, Henket M, Lau L, et al. (2004) Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma. Thorax 59: 111–115.    
  • 14. Kaabachi W, Berraïes A, Dhifallh IB, et al. (2017) Interleukin-26 is overexpressed in Behçet's disease and enhances Th17 related -cytokines. Immunol Lett 190: 177–184.    
  • 15. Wang X, Zhu G, Huang Z, et al. (2012) Application of monoclonal antibodies in a sandwich enzyme-linked immunosorbent assay for identification and detection of soluble human B and T lymphocyte attenuator. Hybridoma 31: 417–423.    
  • 16. Cai G, Freeman GJ (2009) The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunol Rev 229: 244–258.    
  • 17. Oaks MK, Hallett KM, Penwell RT, et al. (2000) A native soluble form of CTLA-4. Cell Immunol 201: 144–153.    
  • 18. Nielsen C, Ohm-Laursen L, Barington T, et al. (2005) Alternative splice variants of the human PD-1 gene. Cell Immunol 235: 109–116.    
  • 19. Magistrelli G, Jeannin P, Herbault N, et al. (1999) A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells. Eur J Immunol 29: 3596–3602.    
  • 20. Chesné J, Braza F, Mahay G, et al. (2014) IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med 190: 1094–1101.
  • 21. Bullens DM, Truyen E, Coteur L, et al. (2006) IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Resp Res 7: 135.    
  • 22. Wu H, Miao M, Zhang G, et al. (2009) Soluble PD-1 isassociated with aberrant regulation of T cells activation in aplasticanemia. Immunol Invest 38: 408–421.    
  • 23. Song MY, Park SH, Nam HJ, et al. (2011) Enhancementof vaccine-induced primary and memory CD8(+) T-cell responsesby soluble PD-1. J Immunother 34: 297–306.    
  • 24. Kuipers H, Muskens F, Willart M, et al. (2006) Contribution of the PD-1 ligands/PD-1 signaling pathway to dendritic cell-mediated CD4+ T cell activation. Eur J Immunol 36: 2472–2482.    
  • 25. Hasegawa T, Uga H, Mori A, et al. (2017) Increased serum IL-17A and Th2 cytokinelevels in patients with severe uncontrolled asthma. Eur Cytokine Netw 28: 8–18.
  • 26. Pyle CJ, Uwadiae FI, Swieboda DP, et al. (2017) Early IL-6 signalling promotesIL-27 dependent maturation of regulatory T cells in the lungs and resolution ofviral immunopathology. PLoS Pathog 13: e1006640.    
  • 27. Maalmi H, Beraies A, Charad R, et al. (2014) IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia. J Asthma 51: 348–354.    
  • 28. Charrad R, Kaabachi W, Berraies A, et al. (2017) IL-33 gene variants and protein expression in pediatric Tunisian asthmatic patients. Cytokine 11: 32.
  • 29. Chen JH, Qin L, Shi YY, et al. (2016) IL-17 protein levels in both induced sputum and plasma are increased in stable but not acute asthma individuals with obesity. Resp Med 121: 48–58.    
  • 30. Lindén A, Dahlén B (2014) Interleukin-17 cytokine signalling in patients with asthma. Eur Respir J 44: 1319–1331.    
  • 31. Ricciardolo FL, Sorbello V, Folino A, et al. (2017) Identification of IL-17F/frequent exacerbator endotype in asthma. J Allergy Clin Immunol 140: 395–406.    
  • 32. Griffiths KL, Khader SA (2014) Bringing in the cavalry: IL-26 mediates neutrophil recruitment to the lungs. Am J Respir Crit Care Med 190: 1079–1080.    
  • 33. Ohnuma K, Hatano R, Aune TM, et al. (2015). Regulation of pulmonary graft-versus-host disease by IL- 26+CD26+CD4 T lymphocytes. J Immunol 194: 3697–3712.    
  • 34. Burlingham WJ, Love RB, Jankowskagan E, et al. (2007) IL-17-dependent cellular immunity to collagen Type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 117: 3498–3506.    
  • 35. Che KF, Tengvall S, Levanen B, et al. (2014) Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization. Am J Respir Crit Care Med 190: 1022–1031.    
  • 36. Elgaili AA, Nzungize L, Duan X, et al. (2016) Interleukin-10 family and tuberculosis: Old story renewed. Int J Biol Sci 12: 710–717.    
  • 37. Charrad R, Kaabachi W, Rafrafi A, et al. (2017) IL-8 gene variants and expression in childhood asthma. Lung 195: 1–9.    

 

Reader Comments

your name: *   your email: *  

© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved