Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways
| Autor: | Adam Chaker, Carsten B. Schmidt-Weber, Ferdinand Guerth, Larissa Lewitan, Moritz Ulrich, Madlen Oelsner, Ulrich M. Zissler, Sandra Rothkirch, Holger Garn, Constanze A. Jakwerth, Miodrag Davidovic |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Allergen immunotherapy medicine.medical_treatment Immunology Respiratory System medicine.disease_cause Transcriptome 03 medical and health sciences 0302 clinical medicine Allergen Allergen-specific Immunotherapy Allergic Rhinitis Asthma Induced Sputum tolerance Immunology and Allergy Medicine Humans Uteroglobin Interleukin 8 business.industry Microarray analysis techniques Rhinitis Allergic Seasonal Immunotherapy Allergens medicine.disease respiratory tract diseases ddc 030104 developmental biology 030228 respiratory system Desensitization Immunologic Sputum Hay fever medicine.symptom business |
| Zdroj: | Allergy 76, 2461-2474 (2021) |
| ISSN: | 1398-9995 |
| Popis: | Background While several systemic immunomodulatory effects of allergen-specific immunotherapy (AIT) have been discovered, local anti-inflammatory mechanisms in the respiratory tract are largely unknown. We sought to elucidate local and epithelial mechanisms underlying allergen-specific immunotherapy in a genome-wide approach. Methods We induced sputum in hay fever patients and healthy controls during the pollen peak season and stratified patients by effective allergen immunotherapy or as untreated. Sputum was directly processed after induction and subjected to whole transcriptome RNA microarray analysis. Nasal secretions were analyzed for Secretoglobin1A1 (SCGB1A1) and IL-24 protein levels in an additional validation cohort at three defined time points during the 3-year course of AIT. Subsequently, RNA was extracted and subjected to an array-based whole transcriptome analysis. Results Allergen-specific immunotherapy inhibited pro-inflammatory CXCL8, IL24, and CCL26mRNA expression, while SCGB1A1, IL7, CCL5, CCL23, and WNT5BmRNAs were induced independently of the asthma status and allergen season. In our validation cohort, local increase of SCGB1A1 occurred concomitantly with the reduction of local IL-24 in upper airways during the course of AIT. Additionally, SCGB1A1 was identified as a suppressor of epithelial gene expression. Conclusions Allergen-specific immunotherapy induces a yet unknown local gene expression footprint in the lower airways that on one hand appears to be a result of multiple regulatory pathways and on the other hand reveals SCGB1A1 as novel anti-inflammatory mediator of long-term allergen-specific therapeutic intervention in the local environment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text