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Jakwerth, C.A. ; Illi, S. ; Charles, H. ; Oelsner, M. ; Gabr, A.A. ; Zissler, U.M. ; Erb, A. ; Feuerherd, M. ; Drost, F. ; Büttner, M. ; Schubert, B. ; Maison, N. ; Omony, J. ; Weckmann, M.* ; Grychtol, R.* ; Dittrich, A.M.* ; Foth, S.* ; Skevaki, C.* ; Trojan, T.* ; van Koningsbruggen-Rietschel, S.* ; Hansen, G.* ; Bahmer, T.* ; Rabe, K.F.* ; Brinkmann, F.* ; Kopp, M.V.* ; Protzer, U. ; Chaker, A. ; Schaub, B.* ; von Mutius, E. ; Schmidt-Weber, C.B.

Nasal epithelial immune signatures are associated with age-dependent asthma trajectories in early life.

Allergy, DOI: 10.1111/all.70477 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND: Preschool wheeze is heterogeneous and only a subset of children progresses to persistent asthma. We hypothesized that early-life wheeze reflects divergent airway epithelial maturation trajectories associated with distinct mucosal immune programs. METHODS: Nasal epithelial transcriptomes from 265 children and young adults (79 healthy, 81 wheezers, 105 asthmatics; median age 10.4 [1.1-20.3] years) from the All Age Asthma Cohort (ALLIANCE) cohort were analyzed using a hypothesis-driven candidate approach based on predefined cytokine axes. Transcriptional signatures were mapped to epithelial cells by scRNA-sequencing. Asthma-outcome associations were assessed in age- and sensitization-adjusted multivariate models. RESULTS: The candidate approach identified three antagonistic epithelial immune programs: an interferon-associated (E1; IDO1, CSF3, CCL20), a type-2-associated (E2; POSTN, CCL26, CST1), and a type-17-associated program (E3; IL36G, KLK7, KRTDAP). These programs were detected across basal, ciliated, and secretory epithelial cells. In early childhood (1-3 years), wheezers predominantly exhibited E1/E3-dominant epithelial profiles (n = 36). Age-group-specific comparisons showed higher E2 and lower E1/E3 expression in wheezers aged 4-6 years (n = 38) than in those aged 1-3 years (n = 36). E2 dominance correlated with IgE, FeNO, and eosinophilia (p < 0.01). In multivariate models assessing asthma outcome at age 6, E1 expression was inversely associated with asthma persistence (OR = 0.15, p < 0.05), whereas E3 expression was associated with disease progression (OR = 4.93, p < 0.05). The combined epithelial signature discriminated asthma outcomes with high accuracy (AUC = 0.90), independent of allergic sensitization. CONCLUSION: Early-life wheeze reflects distinct airway epithelial immune programs characterized by age-associated patterns in epithelial immune activity. Nasal epithelial transcriptional signatures capture molecular trajectories associated with asthma persistence and may enable early risk stratification. TRIAL REGISTRATION: All-Age-Asthma (ALLIANCE) cohort: clinicaltrials.gov: NCT02496468; adult arm: NCT02419274.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Airway Epithelium ; Asthma ; Early Life Wheeze ; Epithelial Immunity ; Nasal Transcriptomics ; Type‐2 Inflammation; Barrier Function; Mucus
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) Institute of Allergy Research (IAF)
Institute for Asthma and Allergy Prevention (IAP)
Institute of Virology (VIRO)
Institute of Computational Biology (ICB)
Grants Universities Giessen and Marburg Lung Center (UGMLC), University Hospital Giessen and Marburg (UKGM) Research
Helmholtz Association under the joint research school "Munich School for Data Science - MUDS"
Joachim Herz Stiftung