{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:27:06Z","timestamp":1789619226912,"version":"build-2803163510"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","award":["PTR (18-16)"],"award-info":[{"award-number":["PTR (18-16)"]}],"id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANR","award":["18-CE14-0020"],"award-info":[{"award-number":["18-CE14-0020"]}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2024,7,9]]},"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)\/receptor-interacting serine\/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air\u2013liquid interface epithelial cultures from asthma patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine\/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air\u2013liquid interface epithelial cultures from asthma patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.02288-2023","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:05:28Z","timestamp":1723129528000},"page":"2302288","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Local receptor-interacting protein kinase 2 inhibition mitigates house dust mite-induced asthma"],"prefix":"10.1183","volume":"64","author":[{"given":"Daniel","family":"Alvarez-Simon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saliha","family":"Ait Yahia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Audousset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Fanton d'Andon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Chamaillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Gomperts Boneca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Tsicopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"2024112623035576000_64.4.2302288.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.10.012"},{"key":"2024112623035576000_64.4.2302288.2","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The cytokines of asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"2024112623035576000_64.4.2302288.3","doi-asserted-by":"crossref","first-page":"662378","DOI":"10.3389\/falgy.2021.662378","article-title":"Characterization of innate immune responses to house dust mite allergens: pitfalls and limitations","volume":"2","author":"Jacquet","year":"2021","journal-title":"Front Allergy"},{"key":"2024112623035576000_64.4.2302288.4","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jaci.2020.12.649","article-title":"NOD1 sensing of house dust mite\u2013derived microbiota promotes allergic experimental asthma","volume":"148","author":"Ait Yahia","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2024112623035576000_64.4.2302288.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084677"},{"key":"2024112623035576000_64.4.2302288.6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi087"},{"key":"2024112623035576000_64.4.2302288.7","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1164\/rccm.201310-1827OC","article-title":"CCL17 production by dendritic cells is required for NOD1-mediated exacerbation of allergic asthma","volume":"189","author":"Ait Yahia","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"2024112623035576000_64.4.2302288.8","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4HI0118-017RR"},{"key":"2024112623035576000_64.4.2302288.9","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxz045"},{"key":"2024112623035576000_64.4.2302288.10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bbrc.2018.02.034","article-title":"RIP2 enhances cell survival by activation of NF-\u0138B in triple negative breast cancer cells","volume":"497","author":"Jaafar","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2024112623035576000_64.4.2302288.11","first-page":"2915","article-title":"RIP2 promotes glioma cell growth by regulating TRAF3 and activating the NF-\u03baB and p38 signaling pathways","volume":"39","author":"Cai","year":"2018","journal-title":"Oncol Rep"},{"key":"2024112623035576000_64.4.2302288.12","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2000073"},{"key":"2024112623035576000_64.4.2302288.13","unstructured":"ClinicalTrials.gov . 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