Sputum IL-26 Is Overexpressed in Severe Asthma and Induces Proinflammatory Cytokine Production and Th17 Cell Generation: A Case–Control Study of Women
Received 2 September 2019
Accepted for publication 12 January 2020
Published 3 February 2020 Volume 2020:13 Pages 95—107
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Amrita Dosanjh
Sabrine Louhaichi, 1–3 Mona Mlika, 2, 4 Besma Hamdi, 1–3 Kamel Hamzaoui, 1, 2 Agnès Hamzaoui 1–3
1Research Laboratory 19SP02 “Chronic Pulmonary Pathologies: From Genome to Management”, Abderrahman Mami Hospital, Ariana, Tunisia; 2Medicine Faculty of Tunis, Department of Basic Sciences, Tunis El Manar University, Tunis, Tunisia; 3Department of Paediatric and Respiratory Diseases, Abderrahman Mami Hospital, Pavillon B, Ariana, Tunisia; 4Pathology Department, Abderrahman Mami Hospital, Ariana, Tunisia
Correspondence: Agnès Hamzaoui
Department of Paediatric and Respiratory Diseases, A. Mami Hospital, Pavillon B, Ariana, Tunisia
Objective: Asthma inflammation is a complex pathway involving numerous mediators. Interleukin-26 (IL-26), a member of the IL-10 cytokine family, is abundant in human airways and induces the production of proinflammatory cytokines. Our aim was to investigate the possible role of IL-26 in severe asthma. We analysed the expression of IL-26 in severe asthma both in peripheral blood and induced sputum.
Patients and Methods: A total of 50 adult women with severe asthma were recruited and compared to 30 healthy controls (HC). Serum and sputum fluid (SF) levels of IL-26 and IL-17 were defined by ELISA. IL-26 mRNA expression and IL-26 protein were analysed using RT-PCR and Western blot. In vitro, we studied the effect of recombinant IL-26 (rIL-26) and SF-IL-26 on cultured CD4+ T cells and monocytes, comparing patients and controls.
Results: Concentrations of IL-26 are higher in serum and induced sputum of asthmatic patients than in HC. Moreover, IL-26 protein and mRNA expression were significantly elevated in asthma sputum cells compared to PBMCs. We observed a positive correlation between body mass index (BMI) and sputum fluid IL-26, while the correlation between IL-26 and lung function tests (FEV1% and FEV1/FVC ratio) was negative. IL-17A was highly expressed in SF and correlated positively with IL-26. In patients’ sputum IL-26 and IL-17A were significantly associated with neutrophils. Stimulation of cultured CD4+ T cells with monocytes by recombinant IL-26 promoted the generation of RORγt+ Th17+ cells inducing the production of IL-17A, IL-1β, IL-6 and TNF-α cytokines. IL-26 expressed in SF was biologically active and induced IL-17 secretion in the presence of IL-1β and IL-6 cytokines.
Conclusion: These findings show that IL-26 is highly produced in asthmatic sputum, induces pro-inflammatory cytokine secretion by monocytes/macrophages, and favours Th17 cell generation. IL-26 thereby appears as a novel pro-inflammatory cytokine, produced locally in the airways that may constitute a promising target to treat asthma inflammatory process.
Keywords: asthma, induced sputum, IL-26, IL-17A, IL-6, IL-1β
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