Air Pollution Drives Macrophage Senescence through a Phagolysosome-15-Lipoxygenase Pathway.

Urban particulate matter (PM; uPM) poses significant health risks, particularly to the respiratory system. Fine particles, such as PM2.5, can penetrate deep into the lungs and exacerbate a range of health problems, including emphysema, asthma, and lung cancer.

Air pollution drives macrophage senescence through a phagolysosome-15-lipoxygenase pathway.

Urban particulate matter (uPM) poses significant health risks, particularly to the respiratory system. Fine particles, such as PM, can penetrate deep into the lungs and exacerbate a range of health problems, including emphysema, asthma, and lung cancer. PM exposure is also linked to extra-pulmonary disorders like heart and neurodegenerative diseases.

Epigenetic regulation of epithelial dectin-1 through an IL-33-STAT3 axis in allergic disease.

Allergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti-inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin-1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients.

NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes.

Purpose: Stabilization of the transcription factor NRF2 through genomic alterations in and occurs in a quarter of patients with lung adenocarcinoma and a third of patients with lung squamous cell carcinoma. In lung adenocarcinoma, loss often co-occurs with loss and -activating alterations. Despite its prevalence, the impact of NRF2 activation on tumor progression and patient outcomes is not fully defined.

Interleukin 13 (IL-13) alters hypoxia-associated genes and upregulates CD73.

Background: Interleukin 13 (IL-13) is a pleiotropic cytokine that has been shown to be important in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and other type 2 inflammation-related diseases. Increased IL-13 expression can elicit several pro-inflammatory effects, including eosinophilia, and pathology such as increased mucus secretion. Polypogenesis in chronic rhinosinusitis (CRS) can be caused by hypoxia, which can also lead to hyperpermeability of airway epithelium and epithelium-to-mesenchymal translation through the upregulation of hypoxia-associated genes, such as HIF1.

Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13).

C3a is required for ILC2 function in allergic airway inflammation.

Aberrant type 2 responses underlie the pathologies in allergic diseases like asthma, yet, our understanding of the mechanisms that drive them remains limited. Recent evidence suggests that dysregulated innate immune factors can perpetuate asthma pathogenesis. In susceptible individuals, allergen exposure triggers the activation of complement, a major arm of innate immunity, leading to the aberrant generation of the C3a anaphylatoxin.

Dysregulated invertebrate tropomyosin-dectin-1 interaction confers susceptibility to allergic diseases.

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells.

Unique pulmonary immunotoxicological effects of urban PM are not recapitulated solely by carbon black, diesel exhaust or coal fly ash.

Background: Exposure to particulate matter (PM) is increasing worldwide as a result of increased human activity, the rapid industrialization of developing countries, and effects of climate change. Adverse effects of PM on human health are well documented, and because PM exposure occurs mostly through the airways, PM has especially deleterious impact on the lungs.

Objective: We investigated whether surrogate PM particles like carbon black (CB), diesel exhaust particle (DEP), coal fly ash (CFA) can recapitulate the allergic airway inflammatory response induced by urban particulate matter.

Epithelial Cell Regulation of Allergic Diseases.

Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental stimuli. Why only certain individuals mount inappropriate type 2 immune responses to these otherwise harmless allergens has remained an unanswered question. Mounting evidence suggests that the epithelium, by sensing its environment, is the central regulator of allergic diseases.

Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica.

Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of bone marrow in SFB-mediated protection.

IL-17A enhances IL-13 activity by enhancing IL-13-induced signal transducer and activator of transcription 6 activation.

Background: Increased IL-17A production has been associated with more severe asthma; however, the mechanisms whereby IL-17A can contribute to IL-13-driven pathology in asthmatic patients remain unclear.

Objective: We sought to gain mechanistic insight into how IL-17A can influence IL-13-driven responses.

Methods: The effect of IL-17A on IL-13-induced airway hyperresponsiveness, gene expression, mucus hypersecretion, and airway inflammation was assessed by using in vivo models of IL-13-induced lung pathology and in vitro culture of murine fibroblast cell lines and primary fibroblasts and human epithelial cell lines or primary human epithelial cells exposed to IL-13, IL-17A, or both.

Differential control of CD4(+) T-cell subsets by the PD-1/PD-L1 axis in a mouse model of allergic asthma.

Studies examining the role of PD-1 family members in allergic asthma have yielded conflicting results. Using a mouse model of allergic asthma, we demonstrate that blockade of PD-1/PD-L1 has distinct influences on different CD4(+) T-cell subsets. PD-1/PD-L1 blockade enhances airway hyperreactivity (AHR), not by altering the magnitude of the underlying Th2-type immune response, but by allowing the development of a concomitant Th17-type immune response.

New twist on an ancient innate immune pathway.

Activation of the complement system has long been known to be regulated by a series of steps involving fluid-phase convertases. In this issue of Immunity, Liszewski et al. (2013) report the discovery of an intracellular cathepsin-L-dependent C3 activation pathway.

Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma.

Severe asthma is associated with the production of interleukin 17A (IL-17A). The exact role of IL-17A in severe asthma and the factors that drive its production are unknown. Here we demonstrate that IL-17A mediated severe airway hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13-driven responses.

Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.

Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs "pro-asthmatic", and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs.

Induction of cyclo-oxygenase-2 expression in naturally occurring gastric ulcers.

Cyclo-oxygenase-2 (COX-2) is believed to participate in the repair of gastric ulcer. Like humans, pigs frequently develop gastric ulcers and thus represent an attractive animal model in which to study the repair process of naturally occurring gastric ulcers. However, expression of COX in the pig stomach has not been reported.