Mast cells and endothelial cells mediate interleukin-33 and ST2 responses in distal chronic obstructive pulmonary disease lungs
(2026) In American Journal of Respiratory and Critical Care Medicine 212(7). p.1495-1509- Abstract
RATIONALE: Information is missing on the tissue cell expression patterns of interleukin 33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and chronic obstructive pulmonary disease (COPD) lungs.
OBJECTIVES: To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls.
METHODS: Surgically excised lung tissue was collected from 38 COPD patients and 21 non-COPD controls. Lung compartment expression of IL-33 and ST2 and key expressing cell types were assessed histologically by combined in situ hybridization and multiplex immunohistochemistry. Expression dynamics of IL-33,... (More)
RATIONALE: Information is missing on the tissue cell expression patterns of interleukin 33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and chronic obstructive pulmonary disease (COPD) lungs.
OBJECTIVES: To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls.
METHODS: Surgically excised lung tissue was collected from 38 COPD patients and 21 non-COPD controls. Lung compartment expression of IL-33 and ST2 and key expressing cell types were assessed histologically by combined in situ hybridization and multiplex immunohistochemistry. Expression dynamics of IL-33, ST2L, and sST2 were explored by spatially resolved single-cell analysis.
MEASUREMENTS AND MAIN RESULTS: COPD lungs displayed increased IL-33 mRNA and IL-33 mRNA/protein ratios, suggesting increased IL-33 turnover. Total ST2/IL1RL1 mRNA levels were upregulated in COPD lungs. Mast cells constituted the major ST2-expressing immune cell population in controls and displayed a microenvironmental-specific upregulation of both ST2L and sST2 in COPD. In control alveolar regions, ST2Lhigh sST2high mast cells were present alongside IL-33-expressing general capillary (gCap) and sST2moderate ST2Llow aerocyte endothelial subsets. In COPD, patchy alveolar regions displayed markedly elevated capillary sST2 and numbers of ST2L+ and IL-33+ gCaps.
CONCLUSIONS: By unraveling the expression patterns of IL-33 and the biologically opposing ST2L and sST2 splice variants in control and COPD lungs, the present study provides novel insights into IL-33-mediated immunity in the distal lung, information that has bearing on treatment strategies targeting this pathway in lung diseases.
(Less)
- author
- Andersson, Cecilia K
LU
; Siddhuraj, Premkumar
LU
; Jönsson, Jimmie
; Ahlgren, Johan
LU
; Lindö, Caroline
LU
; Nys, Josquin A
; Scott, Ian C
; Lindstedt, Sandra
LU
; Kolbeck, Roland
; Humbles, Alison A
; Lutter, René
; Sabogal Piñeros, Yanaika S
; Jonkers, René E
; Tufvesson, Ellen
LU
; Sandén, Caroline
LU
; Cohen, E Suzanne
and Erjefält, Jonas S
LU
(Less) - organization
-
- Paediatric Endocrinology (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Airway Inflammation and Immunology (research group)
- Clinical and experimental lung transplantation (research group)
- LUCC: Lund University Cancer Centre
- WCMM-Wallenberg Centre for Molecular Medicine
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- NPWT technology (research group)
- DCD transplantation of lungs (research group)
- Lung physiology and biomarkers (research group)
- Neonatology (research group)
- Infect@LU
- publishing date
- 2026-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Pulmonary Disease, Chronic Obstructive/metabolism, Interleukin-33/metabolism, Interleukin-1 Receptor-Like 1 Protein, Mast Cells/metabolism, Male, Female, Aged, Middle Aged, Endothelial Cells/metabolism, Lung/metabolism, Receptors, Cell Surface/metabolism, Interleukins, RNA, Messenger/metabolism, Case-Control Studies
- in
- American Journal of Respiratory and Critical Care Medicine
- volume
- 212
- issue
- 7
- pages
- 1495 - 1509
- publisher
- American Thoracic Society
- external identifiers
-
- pmid:42085217
- scopus:105043547303
- ISSN
- 1535-4970
- DOI
- 10.1093/ajrccm/aamag079
- language
- English
- LU publication?
- yes
- additional info
- © The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society.
- id
- 340e9256-7972-4745-ba7b-675edee9e2a1
- date added to LUP
- 2026-08-26 10:50:47
- date last changed
- 2026-08-27 04:00:52
@article{340e9256-7972-4745-ba7b-675edee9e2a1,
abstract = {{<p>RATIONALE: Information is missing on the tissue cell expression patterns of interleukin 33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and chronic obstructive pulmonary disease (COPD) lungs.</p><p>OBJECTIVES: To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls.</p><p>METHODS: Surgically excised lung tissue was collected from 38 COPD patients and 21 non-COPD controls. Lung compartment expression of IL-33 and ST2 and key expressing cell types were assessed histologically by combined in situ hybridization and multiplex immunohistochemistry. Expression dynamics of IL-33, ST2L, and sST2 were explored by spatially resolved single-cell analysis.</p><p>MEASUREMENTS AND MAIN RESULTS: COPD lungs displayed increased IL-33 mRNA and IL-33 mRNA/protein ratios, suggesting increased IL-33 turnover. Total ST2/IL1RL1 mRNA levels were upregulated in COPD lungs. Mast cells constituted the major ST2-expressing immune cell population in controls and displayed a microenvironmental-specific upregulation of both ST2L and sST2 in COPD. In control alveolar regions, ST2Lhigh sST2high mast cells were present alongside IL-33-expressing general capillary (gCap) and sST2moderate ST2Llow aerocyte endothelial subsets. In COPD, patchy alveolar regions displayed markedly elevated capillary sST2 and numbers of ST2L+ and IL-33+ gCaps.</p><p>CONCLUSIONS: By unraveling the expression patterns of IL-33 and the biologically opposing ST2L and sST2 splice variants in control and COPD lungs, the present study provides novel insights into IL-33-mediated immunity in the distal lung, information that has bearing on treatment strategies targeting this pathway in lung diseases.</p>}},
author = {{Andersson, Cecilia K and Siddhuraj, Premkumar and Jönsson, Jimmie and Ahlgren, Johan and Lindö, Caroline and Nys, Josquin A and Scott, Ian C and Lindstedt, Sandra and Kolbeck, Roland and Humbles, Alison A and Lutter, René and Sabogal Piñeros, Yanaika S and Jonkers, René E and Tufvesson, Ellen and Sandén, Caroline and Cohen, E Suzanne and Erjefält, Jonas S}},
issn = {{1535-4970}},
keywords = {{Humans; Pulmonary Disease, Chronic Obstructive/metabolism; Interleukin-33/metabolism; Interleukin-1 Receptor-Like 1 Protein; Mast Cells/metabolism; Male; Female; Aged; Middle Aged; Endothelial Cells/metabolism; Lung/metabolism; Receptors, Cell Surface/metabolism; Interleukins; RNA, Messenger/metabolism; Case-Control Studies}},
language = {{eng}},
month = {{07}},
number = {{7}},
pages = {{1495--1509}},
publisher = {{American Thoracic Society}},
series = {{American Journal of Respiratory and Critical Care Medicine}},
title = {{Mast cells and endothelial cells mediate interleukin-33 and ST2 responses in distal chronic obstructive pulmonary disease lungs}},
url = {{http://dx.doi.org/10.1093/ajrccm/aamag079}},
doi = {{10.1093/ajrccm/aamag079}},
volume = {{212}},
year = {{2026}},
}