Local Receptor-interacting protein kinase 2 inhibition mitigates HDM-induced asthma

Alvarez-Simon, Daniel; Ait Yahia, Saliha; Fanton- d'Andon, Martine; Mathias, Chamaillard; Boneca Ivo, Gomperts; Tsicopoulos, Anne

Document type :

Autre communication scientifique (congrès sans actes - poster - séminaire...)

Title :

Local Receptor-interacting protein kinase 2 inhibition mitigates HDM-induced asthma

Author(s) :

Alvarez-Simon, Daniel [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Ait Yahia, Saliha [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fanton- d'Andon, Martine [Auteur]
Institut Pasteur [Paris] [IP]
Mathias, Chamaillard [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Boneca Ivo, Gomperts [Auteur]
Institut Pasteur [Paris] [IP]
Tsicopoulos, Anne [Auteur]

Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Conference title :

18th IUIS International Congress of Immunology

City :

Cape Town

Country :

Afrique du Sud

Start date of the conference :

2023-11-27

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BackgroundAsthma is the most common chronic airway disorder. House dust mite (HDM) is the most frequent allergen trigger of asthma with different innate immune mechanisms playing critical roles in outcomes. We recently ...
Show more >BackgroundAsthma is the most common chronic airway disorder. House dust mite (HDM) is the most frequent allergen trigger of asthma with different innate immune mechanisms playing critical roles in outcomes. We recently identified the NOD1/RIPK2 signalling pathway (exhibiting mutations associated with asthma) as a relevant contributor to HDM asthma (Ait Yahia, JACI, 2021).ObjectivesThis study aimed to evaluate the effectiveness of a RIPK2 inhibitor administered locally as a preventive and/or therapeutic approach using an experimental HDM-induced allergic asthma model in Wild-type (WT) and mutant huNOD1 mice, and in in vitro bronchial epithelial cells from asthma patients.MethodsWe administered the RIPK2 inhibitor intra-nasally either preventively or therapeutically in our model. Airway hyperresponsiveness (AHR), bronchoalveolar lavage composition, cytokine expression and mucus production were evaluated, as well as the ex vivo effect of the inhibitor on precision lung cut slices (PLCS). Furthermore, the inhibitor was tested on airway liquid interface (ALI) epithelial cultures from asthma patients and controls, and inflammation assessed.ResultsIn WT mice, local preventive administration of the RIPK2 inhibitor reduced AHR, airway eosinophilia, mucus production, Th2 cytokines and the alarmin IL-33. When administered after the sensitization phase, RIPK2 inhibitor failed to reduce the above parameters, except IL-33. However, in mutant huNOD1 mice, therapeutic local RIPK2 inhibition mitigated all asthma features. Results of PLCS emphasized an early role of IL-33 in the NOD1-dependent response of the epithelium to HDM, and a late effect of NOD1 signalling on IL13 effector response. Mechanistically, RIPK2 inhibitor downregulated a number of mediators in HDM-stimulated ALI epithelial cultures from asthma patients including TSLP and chemokines.ConclusionHere we provide evidence supporting that the local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in asthma.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

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