S100A Alarmins and Thymic Stromal Lymphopoietin (TSLP) Regulation in Severe Asthma Following Bronchial Thermoplasty

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2023 Nov 24

PMID 37996952

Authors

Pierre-Alexandre Gagnon

Martin Klein

John De Vos

Sabrina Biardel

Andreanne Cote

Krystelle Godbout

Michel Laviolette

Catherine Laprise

Said Assou

Jamila Chakir

Affiliations

Soon will be listed here.

Abstract

Rationale: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression, cytokine production and metabolic profile. Despite these observations, biological mechanisms explaining asthma control improvement post-BT are still not well understood.

Objectives: To assess whether BT affects gene signatures in bronchial epithelial cells (BECs).

Methods: In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment.

Measurements And Main Results: Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human β-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33.

Conclusions: These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.

Citing Articles

Bronchial thermoplasty for severe asthma: potential mechanisms and response markers.

ChunXiao L, Xin H, Yun L, BoWen L, KunLu S, JiangTao L Ther Adv Respir Dis. 2024; 18:17534666241266348.

PMID: 39344070 PMC: 11440556. DOI: 10.1177/17534666241266348.

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