Th17-Associated Cytokines in Relation to Dysbiosis for Different Clinical Phenotypes of COPD

There is poor understanding of the malfunction in innate immunity that signifies chronic obstructive pulmonary disease (COPD) and there is no effective therapy against it.

However, an emerging body of evidence indicates that T helper (Th)-17 cells possess high mechanistic relevance in this context.

In this project, we determine whether and how Th17-associated cytokines (Th17C) relate to clinical phenotypes of COPD, are associated with dysbiosis and antibacterial activity in the airway mucosa and mirror distinct clinical features.

We assess Th17C locally and systemically in relation to alterations in the airway bacteriome among carefully characterized current long-term smokers (LTS) who have COPD, with or without chronic bronchitis and emphysema, in comparison with LTS without COPD, former LTS with COPD and non-smokers. We quantify Th17C in bronchoalveolar and nasal lavage, mucosal tissue, saliva and blood samples.

We define how Th17C relate to bacterial pathogens (culture, metagenomics) in bronchial brush and sputum samples, leukocytes and antibacterial activity, lung function, CT imaging, history of exacerbations, symptoms, smoking and disease severity according to GOLD.

In experimental sub-studies on primary human cells, we establish the mechanistic role of tobacco smoke in relation to Th17C.

This project may facilitate precision medicine by identifying targets for individualized diagnosis, monitoring and treatment of more than 500 000 COPD patients in Sweden alone.