STARD7 maintains intestinal epithelial mitochondria architecture, barrier integrity, and protection from colitis.

Susceptibility to inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) is linked with loss of intestinal epithelial barrier integrity and mitochondria dysfunction. Steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain-containing protein 7 (STARD7) is a phosphatidylcholine-specific (PC-specific) lipid transfer protein that transports PC from the ER to the mitochondria, facilitating mitochondria membrane stabilization and respiration function. The aim of this study was to define the contribution of STARD7 in the regulation of the intestinal epithelial mitochondrial function and susceptibility to colitis.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium.

Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice.

In the present studies, the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment alters the microbiome in conjunction with immune responses presents striking data. The overall findings identify that although steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17 expression. Analysis of the lung and gut microbiome suggested that there are differences in RSV exacerbation that are further altered by fluticasone (FLUT) treatment.

RSV enhances bacterial growth in the lung.

Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages.

Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways.

Early-life (EL) respiratory infections increase pulmonary disease risk, especially EL-Respiratory Syncytial Virus (EL-RSV) infections linked to asthma. Mechanisms underlying asthma predisposition remain unknown. In this study, we examined the long-term effects on the lung after four weeks post EL-RSV infection.

Inhibiting retinoic acid signaling in dendritic cells suppresses respiratory syncytial virus infection through enhanced antiviral immunity.

Retinoic acid (RA), controls the immunoregulatory functions of many immune cells, including dendritic cells (DCs), and is important for mucosal immunity. In DCs, RA regulates the expression of pattern recognition receptors and stimulates interferon production. Here, we investigated the role of RA in DCs in mounting immunity to respiratory syncytial virus (RSV).

Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology.

Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein array (RPPA) data showed significantly increased PARP1 phosphorylation in RSV-infected DC.

Workshop report: A study roadmap to evaluate the safety of recombinant human lactoferrin expressed in Komagataella phaffii intended as an ingredient in conventional foods - Recommendations of a scientific expert panel.

Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used a glycoengineered yeast, Komatagaella phaffii, to produce recombinant human lactoferrin (Helaina rhLF, Effera™) that is structurally similar to hmLF with intended uses as a food ingredient.

Respiratory and Gut Microbiome Modification during Respiratory Syncytial Virus Infection: A Systematic Review.

Background: Respiratory syncytial virus (RSV) infection is a major cause of lower respiratory tract infection, especially in infants, and increases the risk of recurrent wheezing and asthma. Recently, researchers have proposed a possible association between respiratory diseases and microbiome alterations. However, this connection has not been fully established.

Early-life pulmonary viral infection leads to long-term functional and lower airway structural changes in the lungs.

Early-life respiratory virus infections have been correlated with enhanced development of childhood asthma. In particular, significant numbers of respiratory syncytial virus (RSV)-hospitalized infants go on to develop lung disease. It has been suggested that early-life viral infections may lead to altered lung development or repair that negatively impacts lung function later in life.

Heavy-chain antibody targeting of CD38 NAD hydrolase ectoenzyme to prevent fibrosis in multiple organs.

The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD to ADP-ribose and nicotinamide, CD38 governs organismal NAD homeostasis and the activity of NAD-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD decline underlying adverse metabolic states, frailty and reduced health span.

Mucosal IgA immune complex induces immunomodulatory responses in allergic airway and intestinal T2 disease.

Background: IgA is the most abundant immunoglobulin at the mucosal surface and although its role in regulating mucosal immunity is not fully understood, its presence is associated with protection from developing allergic disease.

Objective: We sought to determine the role of IgA immune complexes for therapeutic application to mucosal allergic responses.

Methods: Trinitrophenol (TNP)-specific IgA immune complexes were applied, using TNP-coupled ovalbumin (OVA), to airway and gut mucosal surfaces in systemically sensitized allergic animals to regulate allergen challenge responses.

Stem cell factor inhibition reduces Th2 inflammation and cellular infiltration in a mouse model of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a T helper (Th)2-mediated inflammatory disorder characterized endoscopically by eosinophilic infiltration leading to fibrosis of the esophagus. Stem cell factor (SCF), a multifunctional cytokine, is upregulated in several allergic diseases, including in patients with EoE. Mast cells and eosinophils express c-kit, the cell surface receptor for SCF, and have been found to play an important role in EoE.

A steroid-resistant cockroach allergen model is associated with lung and cecal microbiome changes.

The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance.

Transepidermal water loss rises before food anaphylaxis and predicts food challenge outcomes.

BACKGROUNDFood allergy (FA) is a growing health problem requiring physiologic confirmation via the oral food challenge (OFC). Many OFCs result in clinical anaphylaxis, causing discomfort and risk while limiting OFC utility. Transepidermal water loss (TEWL) measurement provides a potential solution to detect food anaphylaxis in real time prior to clinical symptoms.

Trained innate immunity, epigenetics, and food allergy.

In recent years the increased incidence of food allergy in Western culture has been associated with environmental factors and an inappropriate immune phenotype. While the adaptive immune changes in food allergy development and progression have been well-characterized, an increase in innate cell frequency and activation status has also recently received greater attention. Early in prenatal and neonatal development of human immunity there is a reliance on epigenetic and metabolic changes that stem from environmental factors, which are critical in training the immune outcomes.

Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.

This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (RSV) infection of 7-day-old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent manner.

Jagged-1 Reduces Th2 Inflammation and Memory Cell Expansion in Allergic Airway Disease.

Notch ligands present during interactions between T cells and dendritic cells (DCs) dictate cell phenotype through a myriad of effects including the induction of T cell regulation, survival, and cytokine response. The presence of Notch ligands on DCs varies with the context of the inflammatory response; Jagged-1 is constitutively expressed, whereas Delta-like 1 and Delta-like 4 are induced in response to pathogen exposure. Although Delta-like and Jagged ligands send different signals through the same Notch receptor, the role of these two ligands in peripheral T cell immunity is not clear.

Cutting Edge: The Expression of Transcription Inhibitor GFI1 Is Induced by Retinoic Acid to Rein in Th9 Polarization.

IL-9, produced mainly by specialized T cells, mast cells, and group 2 innate lymphoid cells, regulates immune responses, including anti-helminth and allergic responses. Polarization of naive CD4 T cells into IL-9-producing T cells (Th9s) is induced by IL-4 and TGF-β1 or IL-1β. In this article, we report that the transcription factor growth factor-independent 1 transcriptional repressor (GFI1) plays a negative role in mouse Th9 polarization.

Microbiome, Metabolism, and Immunoregulation of Asthma: An American Thoracic Society and National Institute of Allergy and Infectious Diseases Workshop Report.

This report presents the proceedings from a workshop titled "Microbiome, Metabolism and Immunoregulation of Asthma" that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research.

Differences in H3K4me3 and chromatin accessibility contribute to altered T-cell receptor signaling in neonatal naïve CD4 T cells.

Neonatal CD4 T cells have reduced or delayed T-cell receptor (TCR) signaling responses compared with adult cells, but the mechanisms underlying this are poorly understood. This study tested the hypothesis that human neonatal naïve CD4 TCR signaling and activation deficits are related to differences in H3K4me3 patterning and chromatin accessibility. Following initiation of TCR signaling using anti-CD3/anti-CD28 beads, adult naïve CD4 T cells demonstrated increased CD69, phospho-CD3ε and interleukin (IL)-2, tumor necrosis factor-α (TNF-α), interferon-γ and IL-17A compared with neonatal cells.

Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection.

Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide.