Household laundry detergents disrupt barrier integrity and induce inflammation in mouse and human skin.

Background: Epithelial barrier impairment is associated with many skin and mucosal inflammatory disorders. Laundry detergents have been demonstrated to affect epithelial barrier function in vitro using air-liquid interface cultures of human epithelial cells.

Methods: Back skin of C57BL/6 mice was treated with two household laundry detergents at several dilutions.

Spatial transcriptomics combined with single-cell RNA-sequencing unravels the complex inflammatory cell network in atopic dermatitis.

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood.

Methods: Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin.

1,25(OH)D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC: A Study in Cells from Healthy Donors and MS Patients.

Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions.

Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients.

Introduction: Artificial Intelligence (AI) methods are being increasingly investigated as a means to generate predictive models applicable in the clinical practice. In this study, we developed a model to predict the efficacy of immunotherapy (IO) in patients with advanced non-small cell lung cancer (NSCLC) using eXplainable AI (XAI) Machine Learning (ML) methods.

Methods: We prospectively collected real-world data from patients with an advanced NSCLC condition receiving immune-checkpoint inhibitors (ICIs) either as a single agent or in combination with chemotherapy.

Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma.

Background: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma.

Objective: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance.

Methods: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration.

Dysregulation of the epithelial barrier by environmental and other exogenous factors.

The "epithelial barrier hypothesis" proposes that the exposure to various epithelial barrier-damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers.

Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis.

Background: Allergic disorders such as atopic dermatitis (AD) are strongly associated with an impairment of the epithelial barrier, in which tight junctions and/or filaggrin expression can be defective. Skin barrier assessment shows potential to be clinically useful for prediction of disease development, improved and earlier diagnosis, lesion follow-up, and therapy evaluation. This study aimed to establish a method to directly assess the in vivo status of epithelial barrier using electrical impedance spectroscopy (EIS).

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.

The Influence of Dietary Fatty Acids on Immune Responses.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors.

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.

Bacterial secretion of histamine within the gut influences immune responses within the lung.

Background: Histamine is an important immunomodulator influencing both the innate and adaptive immune system. Certain host cells express the histidine decarboxylase enzyme (HDC), which is responsible for catalysing the decarboxylation of histidine to histamine. We and others have shown that bacterial strains can also express HDC and secrete histamine; however, the influence of bacterial-derived histamine on the host immune responses distant to the gut is unclear.

Epigenome-wide association in adipose tissue from the METSIM cohort.

Most epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabolic syndrome traits, we profiled global methylation levels in subcutaneous abdominal adipose tissue.

Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases.

There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively).

Anti-inflammatory therapies of amyotrophic lateral sclerosis guided by immune pathways.

Sporadic ALS patients display heterogeneous immune pathways in peripheral blood mononuclear cells (PBMCs). We tested nine sALS patients and one unaffected identical twin of an index case by RNA-Seq of PBMCs. The inflammatory patients (n = 3) clustered into a subset with an inflammatory Th1/Th17 signature and the non-inflammatory patients (n = 7) into another subset with a B cell signature.

Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation.

Background: Macrophages are key targets of HIV-1 infection. We have previously described that the expression of CC chemokine ligand 2 (CCL2) increases during monocyte differentiation to macrophages and it is further up-modulated by HIV-1 exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral replication in infected macrophages.

Increased circulating levels of vitamin D binding protein in MS patients.

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS.

CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients.

CCL2 plays a pivotal role in the recruitment of different immune cells to sites of inflammation and evidence indicates its involvement in multiple sclerosis (MS) pathogenesis. MS lesions are characterized by an inflammatory infiltrate, whose nature is controlled by chemokines and cytokines, and elevated expression of CCL2 has been found in acute and chronic MS plaques within the brain. Vitamin D deficiency is currently considered one of the main environmental MS risk factors.