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Eosinophils, basophils and type 2 immune microenvironments in COPD-affected lung tissue
- Source :
- The European Respiratory Journal, article-version (VoR) Version of Record
- Publication Year :
- 2019
-
Abstract
- Although elevated blood or sputum eosinophils are present in many patients with 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 Global Initiative for Chronic Obstructive Lung Disease stages 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 type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells. A similarly localised and interleukin-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 is likely to have implications for personalised treatment.<br />Highly localised Th2- and eosinophil-rich pockets were identified in COPD-affected lungs, which increased in number with increasing disease severity and included basophils. This exemplifies a novel type of heterogeneity in the immunopathology of COPD. http://bit.ly/2HexTco
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Eotaxin
Adult
Chemokine CCL11
Male
GATA3 Transcription Factor
03 medical and health sciences
Mice
Pulmonary Disease, Chronic Obstructive
Young Adult
0302 clinical medicine
Immune system
Immunopathology
Medicine
Eosinophilia
Animals
Humans
Pulmonary Eosinophilia
CCL11
Aged
COPD
Smokers
business.industry
Macrophages
COPD and basic science
Innate lymphoid cell
Chemokine CCL24
Original Articles
respiratory system
Middle Aged
medicine.disease
Immunity, Innate
respiratory tract diseases
Basophils
Eosinophils
030104 developmental biology
Basophilia
030228 respiratory system
Immunology
Female
medicine.symptom
business
Biomarkers
Subjects
Details
- ISSN :
- 13993003
- Volume :
- 55
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The European respiratory journal
- Accession number :
- edsair.doi.dedup.....cb3f7fc3f73fec2aadf8842806258e06