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. 2025 Jul;156(1):118-128.
doi: 10.1016/j.jaci.2025.03.017. Epub 2025 Mar 28.

Nasal production of IL-26 involving T cells in smokers with and without chronic obstructive pulmonary disease

Julia Arebro  1 , Nikolaos Pournaras  2 , Patricia Ramos-Ramírez  3 , Eduardo I Cardenas  4 , Elga Bandeira  3 , Karlhans Fru Che  3 , Bettina Brundin  3 , Apostolos Bossios  2 , Reza Karimi  5 , Sven Nyrén  6 , Pär Stjärne  7 , Magnus Sköld  8 , Anders Lindén  2
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Free article

Nasal production of IL-26 involving T cells in smokers with and without chronic obstructive pulmonary disease

Julia Arebro et al. J Allergy Clin Immunol. 2025 Jul.
Free article

Abstract

Background: Novel specific therapy in chronic obstructive pulmonary disease (COPD) will require accessible targets for endotyping to identify responsive patients. It is therefore of interest that IL-26 in the bronchoalveolar space is enhanced and associates with bronchoalveolar pathology among long-term smokers (LTS) with and without COPD.

Objective: We determined whether IL-26 in the nasal cavity can be produced by T cells and associates with bronchoalveolar pathology and clinical symptoms in LTS with and without COPD.

Methods: We characterized LTS with and without COPD plus healthy nonsmokers by radiology, spirometry, modified Medical Research Council scale, and St George Respiratory Questionnaire. We determined extracellular IL-26 concentrations (via ELISA) in nasal (NAL) and bronchoalveolar lavage (BAL) samples, BAL neutrophil counts, and NAL IL-26+ T-cell expression (via flow cytometry).

Results: The NAL IL-26 concentrations were higher in LTS with COPD than in healthy nonsmokers. These enhanced IL-26 concentrations displayed a positive correlation with forced expiratory volume in 1 second/forced vital capacity ratio. The IL-26 protein was expressed in CD4+ and CD8+ T cells, but only a small portion of these cells coexpressed IL-15, IL-17A, or IL-22 in LTS with COPD. In this group, IL-26+ CD3+ T cells displayed a negative correlation with forced expiratory volume in 1 second, as did with extracellular NAL IL-26 concentrations. The relative mean fluorescence intensity for CD8+ T cells displayed a negative correlation with modified Medical Research Council and St George Respiratory Questionnaire score.

Conclusion: In the nasal cavity, IL-26 can be produced by local T cells. This IL-26 reflects bronchoalveolar pathology and clinical symptoms, thereby constituting an accessible target with potential for clinically relevant endotyping in COPD.

Keywords: Bronchoalveolar lavage; COPD; IL-26; bronchoalveolar pathology; lung function; nasal cavity; nasal lavage.

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Conflict of interest statement

Disclosure statement Supported by project grants from the Swedish Heart-Lung Foundation (20210286 to A.L., 20220478 to A.B.), the Swedish Research Council (2021-01527 to A.L.), Region Stockholm (20180088 to A.L.), the Swedish Society for Respiratory Medicine (A.L.), and an unrestricted research grant from Astra Zeneca AB, Sweden (A.L.). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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