Conserved interactions with stromal and immune cells coordinate de novo B-cell lymphopoiesis in fetal intestines.

Recent findings suggest that the small intestine (SI) is a novel site for B cell lymphopoiesis during fetal and neonatal life. However, the unique and/or conserved features that enable B cell development at this site remain unclear. To investigate the molecular and cellular scaffolds for B cell lymphopoiesis in mouse and human fetal intestines we leveraged single-cell RNA sequencing, in situ immunofluorescence, spatial transcriptomics and high-dimensional spectral flow cytometry.

RELA Haploinsufficiency Manifesting as an Atypical Phenotype of Crohn's Disease.

Background: Mutations in RELA, a key component of NF-κB signaling, are associated with dysregulated immune responses and inflammatory disorders. While immunodeficiency phenotypes associated with RELA haploinsufficiency have been reported, gastrointestinal manifestations remain poorly described. This study aimed to characterize the clinical, genomic, and immunological features of a patient presenting with an atypical Crohn's-like phenotype driven by RELA haploinsufficiency.

Early-life human CD8 T cells exhibit rapid, short-lived effector responses and a unique transcription factor landscape.

Neonates and infants are distinct in their clinical and cellular responses to viral infections, with neonatal CD8 T cells displaying innate-like characteristics and a low threshold for T cell receptor activation. However, specific molecular programs that drive these unique responses are incompletely understood, particularly in humans, and targetable pathways to modulate viral illness in this vulnerable population remain to be elucidated. Early-life immune responses may be developmentally programmed to prioritize avoidance of tissue immunopathology, especially while maternal immunoglobulin provides passive immunity.

Single-cell antigen receptor sequencing in pigs with influenza.

Single-cell RNA sequencing (scRNAseq) has accelerated characterizing cellular phenotypes in pigs under healthy and diseased conditions. To pair scRNAseq with immune receptor profiling, we developed porcine-specific T cell receptor (TCR) and B cell receptor (BCR) enrichment primers that are compatible with the 10 × Genomics VDJ sequencing protocol. Using these assays, we profiled the immune repertoire of cryopreserved lung cells from CD1D-expressing and CD1D-deficient pigs after one or two infections with influenza A virus (IAV) to examine whether natural killer T (NKT) cells influence pulmonary TCR and BCR receptor repertoires.

In utero human intestine contains maternally derived bacterial metabolites.

Background: Understanding when host-microbiome interactions are first established is crucial for comprehending normal development and identifying disease prevention strategies. Furthermore, bacterially derived metabolites play critical roles in shaping the intestinal immune system. Recent studies have demonstrated that memory T cells infiltrate human intestinal tissue early in the second trimester, suggesting that microbial components such as peptides that can prime adaptive immunity and metabolites that can influence the development and function of the immune system are also present in utero.

Single-cell analysis of pig lung leukocytes and their response to influenza infection and oseltamivir therapy.

Despite pigs being an important species in influenza A virus (IAV) epidemiology and a reliable preclinical model for human IAV infections, many aspects of the porcine pulmonary immune system remain poorly understood. Here, we characterized the single-cell landscape of lung leukocytes of healthy pigs and then compared them to pigs infected with 2009 pandemic H1N1 IAV with or without oseltamivir antiviral therapy. Our data show conserved features as well as species-specific differences in cell types and cell states compared with human and mouse lung lymphocytes.

Consistent Performance of GPT-4o in Rare Disease Diagnosis Across Nine Languages and 4967 Cases.

Background: Large language models (LLMs) are increasingly used in the medical field for diverse applications including differential diagnostic support. The estimated training data used to create LLMs such as the Generative Pretrained Transformer (GPT) predominantly consist of English-language texts, but LLMs could be used across the globe to support diagnostics if language barriers could be overcome. Initial pilot studies on the utility of LLMs for differential diagnosis in languages other than English have shown promise, but a large-scale assessment on the relative performance of these models in a variety of European and non-European languages on a comprehensive corpus of challenging rare-disease cases is lacking.

A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants.

Extremely premature infants (EPIs) who are born before 30 weeks of gestation are susceptible to infection; however, the trajectory of their peripheral immunity is poorly understood. Here, we undertook longitudinal analyses of immune cells from 250 μl of whole blood at 1 week, 1 month, and 2 months from 10 EPIs and compared these with samples from healthy adults and with preterm and full-term cord blood samples. Single-cell suspensions from individual samples were split to perform single-cell RNA sequencing, T and B cell receptor sequencing, and phosphoprotein mass cytometry.

Interleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice.

Interleukin-10 (IL-10) is an immunomodulatory cytokine critical for intestinal immune homeostasis. IL-10 is produced by various immune cells but IL-10 receptor signaling in intestinal CXCR1 mononuclear phagocytes is necessary to prevent spontaneous colitis in mice. Here, we utilized fluorescent protein reporters and cell-specific targeting and found that Rorc-expressing innate lymphoid cells (ILCs) produce IL-10 in response to anti-CD40-mediated intestinal inflammation.

Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production.

Background And Aims: Necrotizing enterocolitis is a severe gastrointestinal complication of prematurity. Using small intestinal organoids derived from fetal tissue of a gestational age similar to an extremely preterm infant, this study aims to assess the effect of diet on intestinal epithelial growth and differentiation to elucidate the role nutrition type plays in intestinal development and modifies the risk for necrotizing enterocolitis.

Methods: Organoids were cultured for 5 days in growth media and 5 days in differentiation media supplemented 1:40 with 4 different diets: parental milk, donor human milk, standard formula, or extensively hydrolyzed formula.

Single-Cell Antigen Receptor Sequencing in Pigs with Influenza.

Understanding the pulmonary adaptive immune system of pigs is important as respiratory pathogens present a major challenge for swine producers and pigs are increasingly used to model human pulmonary diseases. Single-cell RNA sequencing (scRNAseq) has accelerated the characterization of cellular phenotypes in the pig respiratory tract under both healthy and diseased conditions. However, combining scRNAseq with recovery of paired T cell receptor (TCR) α and β chains as well as B cell receptor (BCR) heavy and light chains to interrogate their repertoires has not to our knowledge been demonstrated for pigs.

In utero human intestine contains maternally derived bacterial metabolites.

Understanding when host-microbiome interactions are first established is crucial for comprehending normal development and identifying disease prevention strategies. Furthermore, bacterially derived metabolites play critical roles in shaping the intestinal immune system. Recent studies have demonstrated that memory T cells infiltrate human intestinal tissue early in the second trimester, suggesting that intestinal immune education begins in utero.

Genome-Wide Analysis and Expression Profiling of Lectin Receptor-like Kinase Genes in Watermelon ().

Watermelon is one of the most important edible plants worldwide. Owing to its special cultivation conditions, watermelon is exposed to many biological and abiotic stresses during its development. Lectin receptor-like kinases (LecRLKs) are plant-specific membrane proteins that play important roles in sensing and responding to environmental stimuli.

Single-cell atlas of the small intestine throughout the human lifespan demonstrates unique features of fetal immune cells.

Proper development of mucosal immunity is critical for human health. Over the past decade, it has become evident that in humans, this process begins in utero. However, there are limited data on the unique features and functions of fetal mucosal immune cells.

Deletion of Vβ3CD4 T cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8 T cells.

In both humans and NOD mice, type 1 diabetes (T1D) develops from the autoimmune destruction of pancreatic beta cells by T cells. Interactions between both helper CD4 and cytotoxic CD8 T cells are essential for T1D development in NOD mice. Previous work has indicated that pathogenic T cells arise from deleterious interactions between relatively common genes which regulate aspects of T cell activation/effector function ( ), peptide presentation (, ), and T cell receptor (TCR) signaling ().

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English.

Comparison of oseltamivir and α-galactosylceramide for reducing disease and transmission in pigs infected with 2009 H1N1 pandemic influenza virus.

Influenza virus infections are a major cause of respiratory disease in humans. Neuraminidase inhibitors (NAIs) are the primary antiviral medication used to treat ongoing influenza infections. However, NAIs are not always effective for controlling virus shedding and lung inflammation.

Evaluating α-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs.

Unlabelled: Natural killer T (NKT) cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses. Several studies have used this approach to adjuvant inactivated and subunit influenza A virus (IAV) vaccines, including to enhance cross-protective influenza immunity. However, less is known about whether α-GalCer can enhance live attenuated influenza virus (LAIV) vaccines, which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating influenza vaccines.

A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs.

Many aspects of the porcine immune system remain poorly characterized, which poses a barrier to improving swine health and utilizing pigs as preclinical models. Here, we employ single-cell RNA sequencing (scRNA-seq) to create a cell atlas of the early-adolescent pig thymus. Our data show conserved features as well as species-specific differences in cell states and cell types compared with human thymocytes.

Biological Control and Plant Growth Promotion by Volatile Organic Compounds of T-51.

spp. are widely used in plant disease control and growth promotion due to their high efficacy and multiple biocontrol mechanisms. T-51 is an effective biocontrol agent against gray mold disease by direct contact.

National Rare Diseases Registry System (NRDRS): China's first nation-wide rare diseases demographic analyses.

Background: China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government's systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the "Rare Diseases Cohort Study" (2016-2020), and publishing its first "Rare Disease Catalog" (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)-China's first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020.