IL-37 ameliorates experimental asthma by inhibiting IL-1
A. Schroeder (Borstel, Germany), L. Lunding (Borstel, Germany), C. Vock (Borstel, Germany), B. Schaub (Munich, Germany), U. Zissler (Munich, Germany), H. Fehrenbach (Borstel, Germany), M. Wegmann (Borstel, Germany)
Source: International Congress 2018 – Novel immunology-based therapies in asthma and COPD
Session: Novel immunology-based therapies in asthma and COPD
Session type: Oral Presentation
Number: 1647
Disease area: Airway diseases
Abstract Introduction
We have previously shown that production of the anti-inflammatory cytokine IL-37 is impaired in allergic asthmatics. Additionally, we could demonstrate that application of IL-37 reduces experimental asthma in mice in an IL-18Ra- and SIGIRR-dependent fashion. Thus, supplementation of IL-37 deficiency could be a novel approach towards asthma therapy.
Aims and objectives
We aim to elucidate how IL-37 unfolds its regulatory effects on asthma pathogenesis.
Methods
Immunohistochemical staining against IL-18Ra and SIGIRR was used to identify target cells for IL-37. Airway epithelial cells (AECs) were isolated via laser capture microdissection and examined by microarray-based gene expression analyses. Mononuclear cells (MNC) were isolated from sensitized mice and allergen-specifically activated. Air-Liquid Interface (ALI) cultures of AECs were stimulated with IL-1ß. Wildtype and IL-1R1-deficient mice underwent induction of experimental asthma and were locally treated with IL-37.
Results
Among others AECs, T helper 2 (Th2) cells, and dendritic cells were identified as target cells for IL-37. Gene array analysis of micro-dissected AECs revealed that IL-37 treatment of animals with experimental asthma lead to differential expression of >90 genes induced by IL-1 signaling. In line with this, IL-37 reduced IL-1ß-induced expression of proinflammatory mediators in ALI cultures. Furthermore, IL-37 reduced production of IL-1ß and Th2 cytokines in MNC. Finally, in contrast to WT mice IL-37 had no therapeutic effect on experimental asthma in mice lacking IL-1R1.
Conclusion
In conclusion, these findings indicate that IL-37 down-regulates allergic airway inflammation by inhibiting the proinflammatory activity of IL-1.
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A. Schroeder (Borstel, Germany), L. Lunding (Borstel, Germany), C. Vock (Borstel, Germany), B. Schaub (Munich, Germany), U. Zissler (Munich, Germany), H. Fehrenbach (Borstel, Germany), M. Wegmann (Borstel, Germany). IL-37 ameliorates experimental asthma by inhibiting IL-1. 1647
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