Transcriptomic Profiles of the Nasal Mucosa Following Birch Pollen Provocation Differ Between Birch Pollen-Allergic and Non-Allergic Individuals.

Abstract

Background: Birch pollen (BP) interacts with airway epithelial cells to cause allergic sensitization and allergy in predisposed individuals. However, the basic mechanisms underlying the clinical effects are poorly understood. Changes in gene expression and cytokine secretion in nasal mucosal cells upon BP exposure were determined in BP-allergic and non-allergic individuals.

Methods: BP-allergic (n = 11) and non-allergic individuals (n = 12) participated in nasal provocations with saline and aqueous BP solution. Nasal scrapings and secretions were obtained at baseline and after BP provocation. Bulk RNA sequencing of the nasal scrapings was performed, and cytokines in nasal secretions were quantified.

Results: After BP challenge, we identified 160 differentially expressed genes (DEGs) in the nasal scrapings of allergic individuals and 44 in non-allergic individuals. DEGs encoding S100 proteins, keratins, small proline-rich repeat proteins, and cytokines were predominantly identified, with proinflammatory cytokine transcripts being upregulated only in the allergic cohort. The top canonical pathways in allergic individuals included granulocyte and agranulocyte adhesion and diapedesis, wound healing, IL-8 signaling, and IL-17-related pathways. Enriched pathways in allergic participants were associated with granulocyte chemotaxis, humoral cell responses, and IL-10, IL-4, and IL-13 signaling and were absent in non-allergic individuals. At baseline and after BP challenge, higher amounts of CCL17, CCL20, CCL26, IL-7, IL-16, and IL-33 were detected in nasal secretions of allergic compared to non-allergic individuals.

Conclusion: Our results highlight the activation of important cellular signaling pathways specific to BP-allergic individuals after BP exposure offering new perspectives for studying key players in BP allergy.