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Eosinophils, basophils, and type 2 immune microenvironments in COPD-affected lung tissue

Jogdand, Prajakta LU ; Siddhuraj, Premkumar LU ; Mori, Michiko LU ; Sanden, Caroline LU ; Jönsson, Jimmie ; Walls, Andrew F. ; Kearley, Jennifer ; Humbles, Alison A. ; Kolbeck, Roland and Bjermer, Leif LU , et al. (2020) In European Respiratory Journal 55(4).
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 hybridization identified immune cells, the type 2 immunity marker GATA3, and eotaxins (CCL11, CCL24). Eosinophils and... (More)

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 hybridization 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.

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Contribution to journal
publication status
published
subject
keywords
Basophils, Chemokine CCL11/24, COPD, Eosinophils, Viruses
in
European Respiratory Journal
volume
55
issue
4
publisher
European Respiratory Society
external identifiers
  • scopus:85083920898
  • pmid:32060064
ISSN
0903-1936
DOI
10.1183/13993003.00110-2019
language
English
LU publication?
yes
id
4de7cdf3-5f77-40c4-8f68-a866c788aa86
date added to LUP
2020-05-20 14:40:20
date last changed
2024-06-27 18:07:01
@article{4de7cdf3-5f77-40c4-8f68-a866c788aa86,
  abstract     = {{<p>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 hybridization 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<sup>+</sup> cells, including Th<sub>2</sub> 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<sup>+</sup> fibroblasts and CCL24<sup>+</sup> 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.</p>}},
  author       = {{Jogdand, Prajakta and Siddhuraj, Premkumar and Mori, Michiko and Sanden, Caroline and Jönsson, Jimmie and Walls, Andrew F. and Kearley, Jennifer and Humbles, Alison A. and Kolbeck, Roland and Bjermer, Leif and Newbold, Paul and Erjefält, Jonas S.}},
  issn         = {{0903-1936}},
  keywords     = {{Basophils; Chemokine CCL11/24; COPD; Eosinophils; Viruses}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{European Respiratory Society}},
  series       = {{European Respiratory Journal}},
  title        = {{Eosinophils, basophils, and type 2 immune microenvironments in COPD-affected lung tissue}},
  url          = {{http://dx.doi.org/10.1183/13993003.00110-2019}},
  doi          = {{10.1183/13993003.00110-2019}},
  volume       = {{55}},
  year         = {{2020}},
}