CCL17 Production by Dendritic Cells Is Required for NOD1-mediated Exacerbation of Allergic Asthma

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 a...