Nasal production of IL-26 involving T cells in smokers with and without COPD.

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

Objective: To determine 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 non-smokers (HNS) using radiology, spirometry, modified Medical Research Council (mMRC) scale, and St George's Respiratory Questionnaire (SGRQ). We determined extracellular IL-26 concentrations (ELISA) in nasal (NAL) and bronchoalveolar lavage (BAL) samples, BAL neutrophil counts, and NAL IL-26⁺ T cell expression (flow cytometry).

Results: The NAL IL-26 concentrations were higher in LTS with COPD than in HNS. These enhanced IL-26 concentrations displayed a positive correlation with FEV₁/FVC. The IL-26 protein was expressed in CD4⁺ and CD8⁺ T cells, but only a small portion of these cells co-expressed IL-15, IL-17A, or IL-22 in LTS with COPD. In this group, IL-26⁺ CD3⁺ T cells displayed a negative correlation with FEV₁, as did with extracellular NAL IL-26 concentrations. The relative mean fluorescence intensity (rMFI) for CD8⁺ T cells displayed a negative correlation with mMRC and SGRQ 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.