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Schröder, A.* ; Lunding, L.P.* ; Zissler, U.M. ; Vock, C.* ; Webering, S.* ; Ehlers, J.C.* ; Orinska, Z.* ; Chaker, A. ; Schmidt-Weber, C.B. ; Lang, N.J. ; Schiller, H. B. ; Mall, M.A.* ; Fehrenbach, H.* ; Dinarello, C.A.* ; Wegmann, M.*

IL-37 regulates allergic inflammation by counterbalancing pro-inflammatory IL-1 and IL-33.

Allergy, DOI: 10.1111/all.15072 (2021)
Verlagsversion DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: Children with asthma have impaired production of interleukin (IL) 37; in mice IL-37 reduces hallmarks of experimental allergic asthma (EAA). However, it remains unclear how IL-37 exerts its inhibitory properties in asthma. This study aimed to identify the mechanism(s) by which IL-37 controls allergic inflammation. METHODS: IL-37 target cells were identified by single-cell RNA-seq of IL-1R5 and IL-1R8. Airway tissues were isolated by laser capture microdissection and examined by microarray-based gene expression analysis. Mononuclear cells (MNC) and airway epithelial cells (AECs) were isolated and stimulated with allergen, IL-1β or IL-33 together with recombinant human (rh) IL-37. Wild-type, IL-1R1- and IL-33-deficient mice with EAA were treated with rhIL-37. IL-1β, IL-33, and IL-37 levels were determined in sputum and nasal secretions from adult asthma patients without glucocorticoid-therapy. RESULTS: IL-37 target cells included AECs, T cells, and dendritic cells. In mice with EAA, rhIL-37 led to differential expression of >90 genes induced by IL-1β and IL-33. rhIL-37 reduced production of Th2 cytokines in allergen-activated MNCs from wild-type but not from IL-1R1-deficient mice, and inhibited IL-33-induced Th2 cytokine release. Furthermore, rhIL-37 attenuated IL-1β- and IL-33-induced pro-inflammatory mediator expression in murine AEC cultures. In contrast to wild-type mice, hIL-37 had no effect on EAA in IL-1R1- or IL-33-deficient mice. We also observed that expression/production ratios of both IL-1β and IL-33 to IL-37 were dramatically increased in asthma patients compared to healthy controls. CONCLUSION: IL-37 down-regulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1β and IL-33.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Asthma ; Asthma Treatment ; Inflammation ; Interleukin; Airway Epithelial-cells; Asthma Phenotypes; Tnf-alpha; Cluster-analysis; T-cells; Expression; Cytokines; Helper; Interleukin-1; Receptor
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Zeitschrift Allergy
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Förderungen Bundesministerium für Bildung und Forschung
National Institutes of Health
Deutsche Forschungsgemeinschaft
Deutsche Zentrum für Lungenforschung