The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils

EBioMedicine

Vera Vorstandlechner¹  Anja Peterbauer¹  Michael Mildner¹  Akira Shibuya²  Hendrik Jan Ankersmit³  Gabriela Sánchez Acosta³  Lukas Matthäus Altenburger³  Daniel Bormann³  Alfred Gugerell⁴  Martin Direder⁴  Claudia Kitzmüller⁵  Dragan Copic⁵  Maria Laggner⁶  Florian Gruber⁶  Katharina Klas⁶  Barbara Bohle⁶ 

[1] Aposcience AG, Vienna, Austria;Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria;Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, Austria;Department of Dermatology, Medical University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria;Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria;Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria;

关键词: Anti-allergic therapeutic secretome;    Basophil activation;    Birch pollen allergy;    Mast cell degranulation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary:Background: IgE-mediated hypersensitivity is becoming increasingly prevalent and activation of mast cells and basophils represent key events in the pathophysiology of allergy. We have previously reported that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCsec) exerts beneficial anti-inflammatory effects. Yet, its ability to alleviate allergic symptoms has not been investigated so far. Methods: Several experimental in vitro and in vivo models have been used in this basic research study. A murine ear swelling model was used to study the effects of PBMCsec on 48/80-induced mast cell degranulation in vivo. The transcriptional profile of murine mast cells was analysed by single cell RNA sequencing (scRNAseq). Mast cell activation was studied in vitro using primary skin mast cells. Basophils from individuals allergic to birch pollens were used to investigate basophile activation by allergens. Transcriptomic and lipidomic analyses were used to identify mRNA expression and lipid species present in PBMCsec, respectively. Findings: Topical application of PBMCsec on mouse ears (C57BL/6) significantly reduced tissue swelling following intradermal injection of compound 48/80, an inducer of mast cell degranulation. Single cell RNA sequencing of PBMCsec-treated murine dermal mast cells (Balb/c) revealed a downregulation of genes involved in immune cell degranulation and Fc-receptor signalling. In addition, treatment of primary human dermal mast cells with PBMCsec strongly inhibited compound 48/80- and α-IgE-induced mediator release in vitro. Furthermore, PBMCsec remarkably attenuated allergen driven activation of basophils from allergic individuals. Transcriptomic analysis of these basophils showed that PBMCsec downregulated a distinct gene battery involved in immune cell degranulation and Fc-receptor signalling, corroborating results obtained from dermal mast cells. Finally, we identified the lipid fraction of PBMCsec as the major active ingredient involved in effector cell inhibition. Interpretation: Collectively, our data demonstrate that PBMCsec is able to reduce activation of mast cells and basophils, encouraging further studies on the potential use of PBMCsec for treating allergy. Funding: Austrian Research Promotion Agency (852748 and 862068, 2015-2019), Vienna Business Agency (2343727, 2018-2020), Aposcience AG, Austrian Federal Ministry of Education, Science and Research (SPA06/055), Danube Allergy Research Cluster, Austrian Science Fund (I4437 and P32953).

【 授权许可】

Unknown