NDLI: S100A alarmins and thymic stromal lymphopoietin (TSLP) regulation in severe asthma following bronchial thermoplasty

Content Provider	Springer Nature : BioMed Central
Author	Gagnon, Pierre-Alexandre Klein, Martin De Vos, John Biardel, Sabrina Côté, Andréanne Godbout, Krystelle Laviolette, Michel Laprise, Catherine Assou, Said Chakir, Jamila
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.
Related Links	https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-023-02604-1.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12931-023-02604-1
Journal	Respiratory Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-11-23
Access Restriction	Open
Subject Keyword	Pneumology Respiratory System Alarmin Bronchial thermoplasty Severe asthma Pneumology/Respiratory System
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine
Journal Impact Factor	4.7/2023
5-Year Journal Impact Factor	5.3/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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