Inflammatory signatures for eosinophilic vs. XXXX reveal critical regulatory checkpoints.

@entity1 @entity32 @entity13923 @entity6026 @entity55 @entity19 @entity565 @entity1426 @entity619
Contrary to the T-helper (Th)-2 bias and eosinophil-dominated @entity32 encountered in most asthmatic subjects, other @entity1 may exhibit neutrophil-predominant @entity565 subphenotypes, along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated @entity565 subphenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic vs. neutrophilic @entity565 types, we developed an ovalbumin (OVA)-based @entity19 model of neutrophil-dominated @entity55 . 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 @entity565 model. Briefly, @entity19 were OVA sensitized using either @entity13923 (alum) or complete Freund's adjuvants, followed by OVA aerosol challenge. T-cell, granulocyte, and inflammatory mediator profiles were determined, along with alveolar macrophage genomewide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/ complete Freund's adjuvants adjuvant-based sensitization, followed by allergen challenge, elicited a @entity55 that was poorly controlled by @entity619 , 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-y axis and its control by @entity6026 and @entity6026 binding protein, but also in macrophage @entity1426 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 @entity565 .
