Loss of apolipoprotein E contributes to inflammatory macrophage activation and ferroptosis in NSAID-exacerbated respiratory disease.

Background: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by chronic asthma, nasal polyposis, and intolerance of nonsteroidal anti-inflammatory drugs. We recently described aberrant macrophage activation and lipid metabolism in N-ERD; however, local drivers of nasal inflammation in N-ERD are incompletely understood.

Objective: Our aim was to study how apolipoprotein E (ApoE) deficiency in the N-ERD nasal mucosa affects the cross talk and inflammatory activation of macrophages and epithelial cells.

Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease.

Background: Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe type 2 inflammatory condition.

Methods: EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N-ERD patients or healthy controls by size-exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing.

Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma.

Background: Infectious agents can reprogram or "train" macrophages and their progenitors to respond more readily to subsequent insults. However, whether such an inflammatory memory exists in type 2 inflammatory conditions such as allergic asthma was not known.

Objective: We sought to decipher macrophage-trained immunity in allergic asthma.

Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

Background: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which is driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of arachidonic acid metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD.

Objective: This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD.

An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products.

Eicosanoids are key mediators of type-2 inflammation, e.g., in allergy and asthma.

House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions.

Background: Eicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages.

Assembly-induced folding regulates interleukin 12 biogenesis and secretion.

Members of the IL-12 family perform essential functions in immunoregulation by connecting innate and adaptive immunity and are emerging therapeutic targets. They are unique among other interleukins in forming heterodimers that arise from extensive subunit sharing within the family, leading to the production of at least four functionally distinct heterodimers from only five subunits. This raises important questions about how the assembly of IL-12 family members is regulated and controlled in the cell.