Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial.

Background: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.

Research Question: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?

Study Design And Methods: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible.

CD200Fc limits dendritic cell and B-cell activation during chronic allergen exposures.

Allergic asthma is a chronic inflammatory disease characterized by Th2, conventional dendritic cell, and B-cell activation. In addition to excessive inflammation, asthma pathogenesis includes dysregulation of anti-inflammatory pathways, such as the CD200/CD200R pathway. Thus, we investigated whether a CD200R agonist, CD200Fc, could disrupt the inflammatory cascade in chronic allergic asthma pathogenesis using a mice model of experimental asthma.

Co-modulation of T cells and B cells enhances the inhibition of inflammation in experimental hypersensitivity pneumonitis.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease characterized by antigen-triggered neutrophilic exacerbations. Although CD4 T cells are sufficient for HP pathogenesis, this never translated into efficient T cell-specific therapies. Increasing evidence shows that B cells also play decisive roles in HP.

S1P Contributes to Endotoxin-enhanced B-Cell Functions Involved in Hypersensitivity Pneumonitis.

In a proportion of patients with hypersensitivity pneumonitis, the biological and environmental factors that sustain inflammation are ill defined, resulting in no effective treatment option. Bioaerosols found in occupational settings are complex and often include Toll-like receptor ligands, such as endotoxins. How Toll-like receptor ligands contribute to the persistence of hypersensitivity pneumonitis, however, remains poorly understood.

Metabolic Adaptation of Airway Smooth Muscle Cells to an SPHK2 Substrate Precedes Cytostasis.

Thickening of the airway smooth muscle is central to bronchial hyperreactivity. We have shown that the sphingosine analog ()-2-amino-4-(4-heptyloxyphenyl)-2-methylbutanol (AAL-R) can reverse preestablished airway hyperreactivity in a chronic asthma model. Because sphingosine analogs can be metabolized by SPHK2 (sphingosine kinase 2), we investigated whether this enzyme was required for AAL-R to perturb mechanisms sustaining airway smooth muscle cell proliferation.

Organic components of airborne dust influence the magnitude and kinetics of dendritic cell activation.

Bioaerosol exposure in highly contaminated occupational settings is associated with an increased risk of disease. Yet, few determinants allow for accurate prediction of the immunopathogenic potential of complex bioaerosols. Since dendritic cells are instrumental to the initiation of immunopathological reactions, we studied how dendritic cell activation was modified in response to individual agents, combined microbial agents, or air sample eluates from highly contaminated environmental settings.

Loss of OcaB Prevents Age-Induced Fat Accretion and Insulin Resistance by Altering B-Lymphocyte Transition and Promoting Energy Expenditure.

The current demographic shift toward an aging population has led to a robust increase in the prevalence of age-associated metabolic disorders. Recent studies have demonstrated that the etiology of obesity-related insulin resistance that develops with aging differs from that induced by high-calorie diets. Whereas the role of adaptive immunity in changes in energy metabolism driven by nutritional challenges has recently gained attention, its impact on aging remains mostly unknown.

induces a type IV hypersensitivity response in a mouse model of airway inflammation.

Despite improved awareness of work-related diseases and preventive measures, many workers are still at high risk of developing occupational hypersensitivity airway diseases. This stems from a lack of knowledge of bioaerosol composition and their potential effects on human health. Recently, archaea species were identified in bioaerosols, raising the possibility that they play a major role in exposure-related pathology.

FTY720 promotes pulmonary fibrosis when administered during the remodelling phase following a bleomycin-induced lung injury.

Fibrosis complicates numerous pathologies including interstitial lung diseases. Sphingosine analogs such as FTY720 can alleviate lung injury-induced fibrosis in murine models. Contradictorily, FTY720 also promotes in vitro processes normally leading to fibrosis and high doses in vivo foster lung fibrosis by enhancing vascular leakage into the lung.

Non-culturable bioaerosols in indoor settings: Impact on health and molecular approaches for detection.

Despite their significant impact on respiratory health, bioaerosols in indoor settings remain understudied and misunderstood. Culture techniques, predominantly used for bioaerosol characterisation in the past, allow for the recovery of only a small fraction of the real airborne microbial burden in indoor settings, given the inability of several microorganisms to grow on agar plates. However, with the development of new tools to detect non-culturable environmental microorganisms, the study of bioaerosols has advanced significantly.

Increased prevalence of Methanosphaera stadtmanae in inflammatory bowel diseases.

Background: The gut microbiota is associated with the modulation of mucosal immunity and the etiology of inflammatory bowel diseases (IBD). Previous studies focused on the impact of bacterial species on IBD but seldom suspected archaea, which can be a major constituent of intestinal microbiota, to be implicated in the diseases. Recent evidence supports that two main archaeal species found in the digestive system of humans, Methanobrevibacter smithii (MBS) and Methanosphaera stadtmanae (MSS) can have differential immunogenic properties in lungs of mice; with MSS but not MBS being a strong inducer of the inflammatory response.

Microbial contents of vacuum cleaner bag dust and emitted bioaerosols and their implications for human exposure indoors.

Vacuum cleaners can release large concentrations of particles, both in their exhaust air and from resuspension of settled dust. However, the size, variability, and microbial diversity of these emissions are unknown, despite evidence to suggest they may contribute to allergic responses and infection transmission indoors. This study aimed to evaluate bioaerosol emission from various vacuum cleaners.

Archaeal characterization of bioaerosols from cage-housed and floor-housed poultry operations.

Although bioaerosols from both cage-housed (CH) and floor-housed (FH) poultry operations are highly concentrated, the concentrations of dust, endotoxin, and bacteria are significantly higher in FH bioaerosols. Workers from CH operations have reported a greater prevalence of respiratory symptoms. To date, archaea have been examined in swine and dairy bioaerosols but not in poultry bioaerosols.

Characterization of bioaerosols from dairy barns: reconstructing the puzzle of occupational respiratory diseases by using molecular approaches.

To understand the etiology of exposure-related diseases and to establish standards for reducing the risks associated with working in contaminated environments, the exact nature of the bioaerosol components must be defined. Molecular biology tools were used to evaluate airborne bacterial and, for the first time, archaeal content of dairy barns. Three air samplers were tested in each of the 13 barns sampled.

Immunogenic properties of archaeal species found in bioaerosols.

The etiology of bioaerosol-related pulmonary diseases remains poorly understood. Recently, archaea emerged as prominent airborne components of agricultural environments, but the consequences of airway exposure to archaea remain unknown. Since subcomponents of archaea can be immunogenic, we used a murine model to study the pulmonary immune responses to two archaeal species found in agricultural facilities: Methanobrevibacter smithii (MBS) and Methanosphaera stadtmanae (MSS).