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

Prajakta Jogdand, Premkumar Siddhuraj, Michiko Mori, Caroline Sanden, Jimmie Jönsson, Andrew F. Walls, Jennifer Kearley, Alison A. Humbles, Roland Kolbeck, Leif Bjermer, Paul Newbold, Jonas S. Erjefält

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


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.

TidskriftEuropean Respiratory Journal
StatusPublished - 2020

Ämnesklassifikation (UKÄ)

  • Lungmedicin och allergi


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