Skip to main content
Top
Published in: Respiratory Research 1/2022

Open Access 01-12-2022 | Cytokines | Research

Involvement of IL-26 in bronchiolitis obliterans syndrome but not in acute rejection after lung transplantation

Authors: Jesper M. Magnusson, Petrea Ericson, Sara Tengvall, Marit Stockfelt, Bettina Brundin, Anders Lindén, Gerdt C. Riise

Published in: Respiratory Research | Issue 1/2022

Login to get access

Abstract

Background

 The main long-term complication after lung transplantation is bronchiolitis obliterans syndrome (BOS), a deadly condition in which neutrophils may play a critical pathophysiological role. Recent studies show that the cytokine interleukin IL-26 can facilitate neutrophil recruitment in response to pro-inflammatory stimuli in the airways. In this pilot study, we characterized the local involvement of IL-26 during BOS and acute rejection (AR) in human patients.

Method

 From a biobank containing bronchoalveolar lavage (BAL) samples from 148 lung transplant recipients (LTR), clinically-matched patient pairs were identified to minimize the influence of clinical confounders. We identified ten pairs (BOS/non-BOS) with BAL samples harvested on three occasions for our longitudinal investigation and 12 pairs of patients with and without AR. The pairs were matched for age, gender, preoperative diagnosis, type of and time after surgery. Extracellular IL-26 protein was quantified in cell-free BAL samples using an enzyme-linked immunosorbent assay. Intracellular IL-26 protein in BAL cells was determined using immunocytochemistry (ICC) and flow cytometry.

Results

 The median extracellular concentration of IL-26 protein was markedly increased in BAL samples from patients with BOS (p < 0.0001) but not in samples from patients with AR. Intracellular IL-26 protein was confirmed in alveolar macrophages and lymphocytes (through ICC and flow cytometry) among BAL cells obtained from BOS patients.

Conclusions

 Local IL-26 seems to be involved in BOS but not AR, and macrophages as well as lymphocytes constitute cellular sources in this clinical setting. The enhancement of extracellular IL-26 protein in LTRs with BOS warrants further investigation of its potential as a target for diagnosing, monitoring, and treating BOS.
Literature
1.
go back to reference Rana A, Gruessner A, Agopian VG, et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015;150(3):252–9.CrossRef Rana A, Gruessner A, Agopian VG, et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015;150(3):252–9.CrossRef
2.
go back to reference Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002;166(4):440–4.CrossRef Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002;166(4):440–4.CrossRef
3.
go back to reference Burke CM, Theodore J, Dawkins KD, et al. Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest. 1984;86(6):824–9.CrossRef Burke CM, Theodore J, Dawkins KD, et al. Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest. 1984;86(6):824–9.CrossRef
4.
go back to reference Yousem SA, Burke CM, Billingham ME. Pathologic pulmonary alterations in long-term human heart-lung transplantation. Hum Pathol. 1985;16(9):911–23.CrossRef Yousem SA, Burke CM, Billingham ME. Pathologic pulmonary alterations in long-term human heart-lung transplantation. Hum Pathol. 1985;16(9):911–23.CrossRef
5.
go back to reference Cooper JD, Billingham M, Egan T, et al. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 1993;12(5):713–6.PubMed Cooper JD, Billingham M, Egan T, et al. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 1993;12(5):713–6.PubMed
6.
go back to reference Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;21(3):297–310.CrossRef Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;21(3):297–310.CrossRef
7.
go back to reference Stewart S, Fishbein MC, Snell GI, et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007;26(12):1229–42.CrossRef Stewart S, Fishbein MC, Snell GI, et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007;26(12):1229–42.CrossRef
8.
go back to reference Verleden GM, Vos R, De Vleeschauwer SI, et al. Obliterative bronchiolitis following lung transplantation: from old to new concepts? Transplant Int. 2009;22(8):771–9.CrossRef Verleden GM, Vos R, De Vleeschauwer SI, et al. Obliterative bronchiolitis following lung transplantation: from old to new concepts? Transplant Int. 2009;22(8):771–9.CrossRef
9.
go back to reference Verleden GM, Raghu G, Meyer KC, Glanville AR, Corris P. A new classification system for chronic lung allograft dysfunction. J Heart Lung Transplant. 2014;33(2):127–33.CrossRef Verleden GM, Raghu G, Meyer KC, Glanville AR, Corris P. A new classification system for chronic lung allograft dysfunction. J Heart Lung Transplant. 2014;33(2):127–33.CrossRef
10.
go back to reference Bando K, Paradis IL, Similo S, et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg. 1995;110(1):4–13 (discussion 13-14).CrossRef Bando K, Paradis IL, Similo S, et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg. 1995;110(1):4–13 (discussion 13-14).CrossRef
11.
go back to reference Meyer KC, Raghu G, Verleden GM, et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44(6):1479–503.CrossRef Meyer KC, Raghu G, Verleden GM, et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44(6):1479–503.CrossRef
12.
go back to reference Watschinger B. How T cells recognize alloantigen: evidence for two pathways of allorecognition. Nephrol Dial Transplant. 1995;10(9):1556–8.PubMed Watschinger B. How T cells recognize alloantigen: evidence for two pathways of allorecognition. Nephrol Dial Transplant. 1995;10(9):1556–8.PubMed
13.
go back to reference Hodge G, Hodge S, Holmes-Liew CL, Reynolds PN, Holmes M. Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. J Heart Lung Transplant. 2012;31(8):888–95.CrossRef Hodge G, Hodge S, Holmes-Liew CL, Reynolds PN, Holmes M. Bronchiolitis obliterans syndrome is associated with increased peripheral blood natural killer and natural killer T-like granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. J Heart Lung Transplant. 2012;31(8):888–95.CrossRef
14.
go back to reference Che KF, Tengvall S, Linden A. Interleukin-26 in host defense and inflammatory disorders of the airways. Cytokine Growth Factor Rev. 2021;57:1–10.CrossRef Che KF, Tengvall S, Linden A. Interleukin-26 in host defense and inflammatory disorders of the airways. Cytokine Growth Factor Rev. 2021;57:1–10.CrossRef
15.
go back to reference Knappe A, Hor S, Wittmann S, Fickenscher H. Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri. J Virol. 2000;74(8):3881–7.CrossRef Knappe A, Hor S, Wittmann S, Fickenscher H. Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri. J Virol. 2000;74(8):3881–7.CrossRef
16.
go back to reference Hor S, Pirzer H, Dumoutier L, et al. The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. J Biol Chem. 2004;279(32):33343–51.CrossRef Hor S, Pirzer H, Dumoutier L, et al. The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. J Biol Chem. 2004;279(32):33343–51.CrossRef
17.
go back to reference Donnelly RP, Sheikh F, Dickensheets H, Savan R, Young HA, Walter MR. Interleukin-26: an IL-10-related cytokine produced by Th17 cells. Cytokine Growth Factor Rev. 2010;21(5):393–401.CrossRef Donnelly RP, Sheikh F, Dickensheets H, Savan R, Young HA, Walter MR. Interleukin-26: an IL-10-related cytokine produced by Th17 cells. Cytokine Growth Factor Rev. 2010;21(5):393–401.CrossRef
18.
go back to reference Che KF, Tengvall S, Levanen B, et al. Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization. Am J Resp Crit Care Med. 2014;190(9):1022–31.CrossRef Che KF, Tengvall S, Levanen B, et al. Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization. Am J Resp Crit Care Med. 2014;190(9):1022–31.CrossRef
19.
go back to reference DiGiovine B, Lynch JP 3rd, Martinez FJ, et al. Bronchoalveolar lavage neutrophilia is associated with obliterative bronchiolitis after lung transplantation: role of IL-8. J Immunol. 1996;157(9):4194–202.PubMed DiGiovine B, Lynch JP 3rd, Martinez FJ, et al. Bronchoalveolar lavage neutrophilia is associated with obliterative bronchiolitis after lung transplantation: role of IL-8. J Immunol. 1996;157(9):4194–202.PubMed
20.
go back to reference Riise GC, Andersson BA, Kjellstrom C, et al. Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant. Eur Respir J. 1999;14(5):1123–30.CrossRef Riise GC, Andersson BA, Kjellstrom C, et al. Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant. Eur Respir J. 1999;14(5):1123–30.CrossRef
21.
go back to reference Riise GC, Schersten H, Nilsson F, Ryd W, Andersson BA. Activation of eosinophils and fibroblasts assessed by eosinophil cationic protein and hyaluronan in BAL. Association with acute rejection in lung transplant recipients. Chest. 1996;110(1):89–96.CrossRef Riise GC, Schersten H, Nilsson F, Ryd W, Andersson BA. Activation of eosinophils and fibroblasts assessed by eosinophil cationic protein and hyaluronan in BAL. Association with acute rejection in lung transplant recipients. Chest. 1996;110(1):89–96.CrossRef
22.
go back to reference Riise GC, Kjellstrom C, Ryd W, et al. Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study. Eur Respir J. 1997;10(8):1742–6.CrossRef Riise GC, Kjellstrom C, Ryd W, et al. Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study. Eur Respir J. 1997;10(8):1742–6.CrossRef
23.
go back to reference Yousem SA, Berry GJ, Cagle PT, et al. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant. 1996;15(1 Pt 1):1–15.PubMed Yousem SA, Berry GJ, Cagle PT, et al. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant. 1996;15(1 Pt 1):1–15.PubMed
24.
go back to reference Corvaisier M, Delneste Y, Jeanvoine H, et al. IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation. PLoS Biol. 2012;10(9): e1001395.CrossRef Corvaisier M, Delneste Y, Jeanvoine H, et al. IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation. PLoS Biol. 2012;10(9): e1001395.CrossRef
25.
go back to reference Dambacher J, Beigel F, Zitzmann K, et al. The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut. 2009;58(9):1207–17.CrossRef Dambacher J, Beigel F, Zitzmann K, et al. The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut. 2009;58(9):1207–17.CrossRef
26.
go back to reference Tengvall S, Che KF, Linden A. Interleukin-26: an emerging player in host defense and inflammation. J Innate Immun. 2016;8(1):15–22.CrossRef Tengvall S, Che KF, Linden A. Interleukin-26: an emerging player in host defense and inflammation. J Innate Immun. 2016;8(1):15–22.CrossRef
27.
go back to reference Pene J, Chevalier S, Preisser L, et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008;180(11):7423–30.CrossRef Pene J, Chevalier S, Preisser L, et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008;180(11):7423–30.CrossRef
28.
go back to reference Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med. 1999;340(14):1081–91.CrossRef Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med. 1999;340(14):1081–91.CrossRef
30.
go back to reference Che KF, Tufvesson E, Tengvall S, et al. The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers. Clin Sci (Lond). 2018;132(9):959–83.CrossRef Che KF, Tufvesson E, Tengvall S, et al. The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers. Clin Sci (Lond). 2018;132(9):959–83.CrossRef
31.
go back to reference Seok J, Warren HS, Cuenca AG, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA. 2013;110(9):3507–12.CrossRef Seok J, Warren HS, Cuenca AG, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA. 2013;110(9):3507–12.CrossRef
32.
go back to reference Ohnuma K, Hatano R, Aune TM, et al. Regulation of pulmonary graft-versus-host disease by IL-26+CD26+CD4 T lymphocytes. J Immunol. 2015;194(8):3697–712.CrossRef Ohnuma K, Hatano R, Aune TM, et al. Regulation of pulmonary graft-versus-host disease by IL-26+CD26+CD4 T lymphocytes. J Immunol. 2015;194(8):3697–712.CrossRef
33.
go back to reference Benitez A, Weldon AJ, Tatosyan L, et al. Differences in mouse and human nonmemory B cell pools. J Immunol. 2014;192(10):4610–9.CrossRef Benitez A, Weldon AJ, Tatosyan L, et al. Differences in mouse and human nonmemory B cell pools. J Immunol. 2014;192(10):4610–9.CrossRef
Metadata
Title
Involvement of IL-26 in bronchiolitis obliterans syndrome but not in acute rejection after lung transplantation
Authors
Jesper M. Magnusson
Petrea Ericson
Sara Tengvall
Marit Stockfelt
Bettina Brundin
Anders Lindén
Gerdt C. Riise
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2022
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-022-02036-3

Other articles of this Issue 1/2022

Respiratory Research 1/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.