Size of lipid emulsion droplets influences metabolism in human CD4 T cells.

Scope: Triglyceride-based lipid emulsions are critical for total parenteral nutrition (TPN), but their long-term use has adverse effects, such as severe liver dysfunction necessitating improved formulations. This study compares the uptake mechanism and intracellular fate of novel glycerol-stabilized nano-sized lipid emulsions with conventional emulsions in CD4 T cells, focusing on their impact on cellular metabolism.

Methods And Results: Nanoemulsions were formulated with increased glycerol content.

Crosstalk within peripheral blood mononuclear cells mediates anti-inflammatory effects of n-3 PUFA-rich lipid emulsions in parenteral nutrition.

Background And Aims: Parenteral nutrition (PN) rich in n-6 and n-3 long-chain fatty acids is used in clinical practice for nourishing patients who are unable to receive adequate nutrition through their digestive systems. In this study, we compare the effect on inflammation of the commonly used lipid emulsions Omegaven (n-3-rich) and Intralipid (n-6-rich) in human peripheral blood mononuclear cells (PBMCs).

Methods: PBMCs were treated with different doses of n-3-rich Omegaven and n-6-rich Intralipid and the immune cells were characterized by flow cytometry.

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium.

Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium.

SARS-CoV-2 enters human cells through its main receptor, angiotensin-converting enzyme 2 (ACE2), which constitutes a limiting factor of infection. Recent findings demonstrating novel ACE2 isoforms implicate that this receptor is regulated in a more complex way than previously anticipated. However, it remains unknown how various inflammatory conditions influence the abundance of these ACE2 variants.

Novel lipid emulsion for total parenteral nutrition based on 18-carbon n-3 fatty acids elicits a superior immunometabolic phenotype in a murine model compared with standard lipid emulsions.

Background: While lipid emulsions in modern formulations for total parenteral nutrition (TPN) provide essential fatty acids and dense calories, they also promote inflammation and immunometabolic disruptions.

Objectives: We aimed to develop a novel lipid emulsion for TPN use with superior immunometabolic actions compared with available standard lipid emulsions.

Methods: A novel lipid emulsion [Vegaven (VV)] containing 30% of 18-carbon n-3 fatty acids (α-linolenic acid and stearidonic acid) was developed for TPN (VV-TPN) and compared with TPN containing soybean oil-based lipid emulsion (IL-TPN) and fish-oil-based lipid emulsion (OV-TPN).

Lipid emulsion rich in n-3 polyunsaturated fatty acids elicits a pro-resolution lipid mediator profile in mouse tissues and in human immune cells.

Background: Lipid emulsions are a key component of total parenteral nutrition (TPN) and are administered to patients who are unable to ingest their daily required calories orally. Lipid emulsions rich with n-6 (ω-6) PUFAs are known to cause parenteral nutrition-associated liver disease and have inflammatory side effects, whereas n-3 PUFA-rich emulsions have favourable clinical outcomes.

Objectives: The present study used targeted lipid mediator analysis to investigate the metabolism of a n-3 PUFA-rich lipid emulsion and a n-6 PUFA-rich lipid emulsion in a mouse model of TPN and in primary human monocyte-derived macrophages (MDMs) and CD4+ T cells.

The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development.

The respiratory epithelium constitutes the physical barrier between the human body and the environment, thus providing functional and immunological protection. It is often exposed to allergens, microbial substances, pathogens, pollutants, and environmental toxins, which lead to dysregulation of the epithelial barrier and result in the chronic inflammation seen in allergic diseases and asthma. This epithelial barrier dysfunction results from the disturbed tight junction formation, which are multi-protein subunits that promote cell-cell adhesion and barrier integrity.

Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages.

Obesity leads to chronic inflammation of the adipose tissue which is tightly associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of the adipose tissue is mainly characterized by the presence of crown-like structures composed of inflammatory macrophages in the neighborhood of adipocytes. Resolvin D1 (RvD1), a potent anti-inflammatory and pro-resolving lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid, has been shown to reduce the inflammatory tone of adipose tissue in animal models but the underlying mechanism is not clear.

Spermidine and spermine exert protective effects within the lung.

Asthma is a heterologous disease that is influenced by complex interactions between multiple environmental exposures, metabolism, and host immunoregulatory processes. Specific metabolites are increasingly recognized to influence respiratory inflammation. However, the role of protein-derived metabolites in regulating inflammatory responses in the lung are poorly described.

Nutritional Lipids and Mucosal Inflammation.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation in the intestine. Given their role in regulation of inflammation, long-chain n-3 polyunsaturated fatty acids (PUFAs) represent a potential supplementary therapeutic approach to current drug regimens used for IBD. Mechanistically, there is ample evidence for an anti-inflammatory and pro-resolution effect of long-chain n-3 PUFAs after they incorporate into cell membrane phospholipids.

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition.

Scope: The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance.

Methods And Results: Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC).

Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors.

Background: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19.

Outside-in hypothesis revisited: The role of microbial, epithelial, and immune interactions.

Objective: Our understanding of the origin of allergic diseases has increased in recent years, highlighting the importance of microbial dysbiosis and epithelial barrier dysfunction in affected tissues. Exploring the microbial-epithelial-immune crosstalk underlying the mechanisms of allergic diseases will allow the development of novel prevention and treatment strategies for allergic diseases.

Data Sources: This review summarizes the recent advances in microbial, epithelial, and immune interactions in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma.

Novel Strategies to Prevent Total Parenteral Nutrition-Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes.

Total parenteral nutrition (TPN) is a life-saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN-associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described.

Blocking histone deacetylase activity as a novel target for epithelial barrier defects in patients with allergic rhinitis.

Background: A defective epithelial barrier is found in patients with allergic rhinitis (AR) and asthma; however, the underlying mechanisms remain poorly understood. Histone deacetylase (HDAC) activity has been identified as a crucial driver of allergic inflammation and tight junction dysfunction.

Objective: We investigated whether HDAC activity has been altered in patients with AR and in a mouse model of house dust mite (HDM)-induced allergic asthma and whether it contributed to epithelial barrier dysfunction.

Direct assessment of skin epithelial barrier by electrical impedance spectroscopy.

Background: Many skin and mucosal inflammatory disorders, such as atopic dermatitis, have been associated with an impaired epithelial barrier function, which allows allergens, pollutants, or microbes to enter the tissue and activate the immune response. The aim of this study was to establish a method to directly assess in vivo the epidermal barrier function by electrical impedance (EI) spectroscopy.

Methods: Mice epidermal barrier was damaged by epicutaneous application of proteases and cholera toxin and by tape stripping.

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid.

Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized.

Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells.

Background: Defects in the epithelial barrier have recently been associated with asthma and other allergies. The influence of laundry detergents on human bronchial epithelial cells (HBECs) and their barrier function remain unknown.

Objective: We investigated the effects of laundry detergents on cytotoxicity, barrier function, the transcriptome, and the epigenome in HBECs.

Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis.

Background: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and T2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier.

Objective: We sought to investigate the role of histamine and T2 cells in driving epithelial barrier dysfunction in AR.

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis.

miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In this study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in the lesional skin of patients with psoriasis.

Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

Background: Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously.

Objective: We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice.

Methods: Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions.