2026/03/19 by Cecilia K Andersson, Premkumar Siddhuraj, Jimmie Jönsson +14 · 1 voice
Immunology and Microbiology · Medicine · #IL-33, ST2, and ILC Pathways #Eosinophilic Esophagitis #Asthma and respiratory diseases
paper · doi:10.1093/ajrccm/aamag079
openalex publication_date 2026/03/19 · openalex created_date 2026/03/25 · openalex updated_date 2026/07/27
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.