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http://purl.uniprot.org/citations/24661094http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24661094http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Pattern recognition receptors are attractive targets for vaccine adjuvants, and polymorphisms of the innate receptor NOD1 have been associated with allergic asthma.

Objectives

To elucidate whether NOD1 agonist may favor allergic asthma in humans through activation of dendritic cells, and to evaluate the mechanisms involved using an in vivo model.

Methods

NOD1-primed dendritic cells from allergic and nonallergic donors were characterized in vitro on their phenotype, cytokine secretion, and Th2 polarizing ability. The in vivo relevance was examined in experimental allergic asthma, and the mechanisms were assessed using transfer of NOD1-conditioned dendritic cells from wild-type or CCL17-deficient mice.

Measurements and main results

NOD1 priming of human dendritic cells promoted a Th2 polarization profile that involved the production of CCL17 and CCL22 in nonallergic subjects but only CCL17 in allergic patients, without requiring allergen costimulation. Moreover, NOD1-primed dendritic cells from allergic donors exhibited enhanced maturation that led to abnormal CCL22 and IL-10 secretion compared with nonallergic donors. In mice, systemic NOD1 ligation exacerbated allergen-induced experimental asthma by amplifying CCL17-mediated Th2 responses in the lung. NOD1-mediated sensitization of purified murine dendritic cells enhanced production of CCL17 and CCL22, but not of thymic stromal lymphopoietin and IL-33, in vitro. Consistently, adoptive transfer of NOD1-conditioned dendritic cells exacerbated the Th2 pulmonary response in a CCL17-dependent manner in vivo.

Conclusions

Data from this study unveil a deleterious role of NOD1 in allergic asthma through direct induction of CCL17 by dendritic cells, arguing for a need to address vaccine formulation safety issues related to allergy."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.org/dc/terms/identifier"doi:10.1164/rccm.201310-1827oc"xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Fan Y."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Boneca I.G."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Werts C."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Duez C."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Chamaillard M."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Tsicopoulos A."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Grandjean T."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Delacre M."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Fanton d'Andon M."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Vorng H."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Wallaert B."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Chenivesse C."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Ait Yahia S."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Azzaoui I."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Ple C."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Balsamelli J."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Everaere L."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/author"Marquillies P."xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/name"Am J Respir Crit Care Med"xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/pages"899-908"xsd:string
http://purl.uniprot.org/citations/24661094http://purl.uniprot.org/core/title"CCL17 production by dendritic cells is required for NOD1-mediated exacerbation of allergic asthma."xsd:string
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