Abstract
Although elevated blood or sputum eosinophils are present in many patients with chronic obstructive pulmonary disease (COPD), uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils, and eosinophil-promoting immune mechanisms in COPD-affected lungs.
Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades GOLD I–IV; never-smokers/smokers served as controls. Automated immunohistochemistry and in-situ hybridisation identified immune cells, the type 2 immunity marker GATA3, and eotaxins (CCL11, CCL24).
Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+ cells, including Th2 lymphocytes and type 2 innate lymphoid cells. A similarly localised and IL-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11+ fibroblasts and CCL24+ macrophages.
In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that will likely have implications for personalised treatment.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Jogdand has nothing to disclose.
Conflict of interest: Dr. Siddhuraj has nothing to disclose.
Conflict of interest: Dr. Mori has nothing to disclose.
Conflict of interest: Dr. Sanden has nothing to disclose.
Conflict of interest: Dr. Jönsson has nothing to disclose.
Conflict of interest: Dr. Walls has nothing to disclose.
Conflict of interest: Dr. Kearley reports other from MedImmune LLC, other from AstraZeneca, outside the submitted work.
Conflict of interest: Dr. Humbles reports other from MedImmune LLC, other from AstraZeneca, outside the submitted work.
Conflict of interest: Dr. Kolbeck reports other from MedImmune LLC, other from AstraZeneca, outside the submitted work.
Conflict of interest: Dr. Bjermer has nothing to disclose.
Conflict of interest: Dr. Newbold reports other from MedImmune LLC, other from AstraZeneca, outside the submitted work.
Conflict of interest: Dr. Erjefält reports: JE is founder (and stock owner) of Medetect AB who recieved funding from AstraZeneca for conducting parts of the present study.
- Received January 15, 2019.
- Accepted February 5, 2020.
- Copyright ©ERS 2020