Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation
Background Allergic asthma is a chronic disease and medical treatment often fails to fully control the disease in the long term, leading to a great need for new therapeutic approaches. Immunoproteasome inhibition impairs T helper cell function and is effective in many (auto-) inflammatory settings b...
Saved in:
Published in | Frontiers in immunology Vol. 13; p. 870720 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
30.05.2022
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Background
Allergic asthma is a chronic disease and medical treatment often fails to fully control the disease in the long term, leading to a great need for new therapeutic approaches. Immunoproteasome inhibition impairs T helper cell function and is effective in many (auto-) inflammatory settings but its effect on allergic airway inflammation is unknown.
Methods
Immunoproteasome expression was analyzed in
in vitro
polarized T helper cell subsets. To study Th2 cells
in vivo
acute allergic airway inflammation was induced in GATIR (GATA-3-vYFP reporter) mice using ovalbumin and house dust mite extract. Mice were treated with the immunoproteasome inhibitor ONX 0914 or vehicle during the challenge phase and the induction of airway inflammation was analyzed.
Results
In vitro
polarized T helper cell subsets (Th1, Th2, Th17, and Treg) express high levels of immunoproteasome subunits. GATIR mice proved to be a useful tool for identification of Th2 cells. Immunoproteasome inhibition reduced the Th2 response in both airway inflammation models. Furthermore, T cell activation and antigen-specific cytokine secretion was impaired and a reduced infiltration of eosinophils and professional antigen-presenting cells into the lung and the bronchoalveolar space was observed in the ovalbumin model.
Conclusion
These results show the importance of the immunoproteasome in Th2 cells and airway inflammation. Our data provides first insight into the potential of using immunoproteasome inhibition to target the aberrant Th2 response, e.g. in allergic airway inflammation. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Francois DAUBEUF, Université de Strasbourg, France; Silke Meiners, Research Center Borstel (LG), Germany Edited by: In Sik Kim, Eulji University, South Korea This article was submitted to Inflammation, a section of the journal Frontiers in Immunology Present address: Tata Nageswara Rao, Stem Cells and Cancer Biology Laboratory, Department of Oncology and Hematology, Medical Research Center, Cantonal Hospital St. Gallen, St.Gallen, Switzerland |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.870720 |