Reference : Inflammatory signatures for eosinophilic versus neutrophilic allergic pulmonary infla...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Inflammatory signatures for eosinophilic versus neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints.
Bogaert, P. [> >]
Naessens, T. [> >]
De Koker, S. [> >]
Hennuy, B. [> >]
Hacha, Jonathan mailto [Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Smet, M. [> >]
Cataldo, Didier mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
Di Valentin, Emmanuel mailto [Université de Liège - ULiège > > GIGA-R : Virologie - Immunologie >]
Piette, Jacques mailto [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie >]
Tournoy, K. G. [> >]
Grooten, Jean-Marie [> >]
American Journal of Physiology - Lung Cellular and Molecular Physiology
American Physiological Society
sous presse
Yes (verified by ORBi)
[en] neutrophil-predominant asthma ; allergic inflammation ; alveolar macrophage ; transcriptome
[en] Contrarily to the Th-2-bias and eosinophil-dominated bronchial inflammation encountered in most asthmatics, other patients may exhibit neutrophil-predominant asthma sub-phenotypes along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated asthma sub-phenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic versus neutrophilic asthma types, we developed an Ovalbumin (OVA)-based mouse model of neutrophil-dominated allergic pulmonary inflammation. Consequently, we probed for particular inflammatory signatures and checkpoints underlying the immune-pathology in this new model as well as in a conventional, eosinophil-dominated asthma model. Briefly, mice were OVA-sensitized using either aluminium hydroxide (alum) or Complete Freund's (CFA)-adjuvants followed by OVA aerosol challenge. T-cell, granulocyte and inflammatory mediator profiles were determined along with alveolar macrophage genome-wide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/CFA-adjuvant-based sensitization followed by allergen challenge elicited a pulmonary inflammation that was poorly controlled by dexamethasone, and in which Th-1 and Th-17 cells additionally participated. Analysis of the overall pulmonary and alveolar macrophage inflammatory mediator profiles revealed remarkable similarities between both models. Nevertheless, we observed pronounced differences in the IL-12/IFN-γ axis and its control by IL-18 and IL-18 Binding Protein (BP), but also in macrophage arachidonic acid metabolism and expression of T-cell instructive ligands. These differential signatures, superimposed onto a generic inflammatory signature, denote distinctive inflammatory checkpoints potentially involved in orchestrating neutrophil-dominated asthma. Key words: neutrophil-predominant asthma, allergic inflammation, alveolar macrophage, transcriptome, mouse models.

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