Immune landscape of human placental villi using single-cell analysis.

Maintenance of a healthy pregnancy is reliant on a successful balance between the fetal and maternal immune systems. Although the maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV).

Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection.

Background: Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown.

CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged).

Lymphocytic Esophagitis With Predominance of CD4 T Cells and Expansion of Th1 Cells Is Associated With Achalasia.

Objectives: Although histologic features in biopsies suggesting a possibility of achalasia would be helpful diagnostically, such features remain unknown. The goal of this study was to explore the prevalence, histologic features, and immunophenotype of lymphocytic esophagitis (LyE) in achalasia biopsies.

Methods: The study group consisted of 57 patients with achalasia.

Monogenic Inflammatory Bowel Disease: It's Never Too Late to Make a Diagnosis.

More than 50 different monogenic disorders have been identified as directly causing inflammatory bowel diseases, typically manifesting in the first years of life. We present the clinical course and immunological work-up of an adult patient who presented in adolescent years with an atypical gastrointestinal phenotype and was diagnosed more than two decades later with a monogenic disorder with important therapeutic implications. Whole exome sequencing was performed in a 37-years-old patient with a history of diarrhea since adolescence.

In utero human intestine harbors unique metabolome, including bacterial metabolites.

Symbiotic microbial colonization through the establishment of the intestinal microbiome is critical to many intestinal functions, including nutrient metabolism, intestinal barrier integrity, and immune regulation. Recent studies suggest that education of intestinal immunity may be ongoing in utero. However, the drivers of this process are unknown.

Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation.

Intra-amniotic (IA) inflammation is associated with significant morbidities for both the mother and the fetus. Prior studies have illustrated many of the effects of IA inflammation on the uterine lining (decidua) and membranous layers of the placenta at the fetal-maternal interface. However, much less is known about the immunological response occurring within the villous placenta.

Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease.

Background & Aims: Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn's disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution.

Methods: We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls.

Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development.

There are limited data on fetal and early life development of human intestinal immunity. Using mass cytometry (CyTOF) and next-generation sequencing of B and T cell receptor (BCR and TCR) repertoires, we demonstrate complex intestinal immunity from 16 weeks' gestational age (GA). Both BCR and TCR repertoires are diverse with CDRH and CDR3β length increasing with advancing GA.

Interferon Lambda Inhibits Bacterial Uptake during Influenza Superinfection.

Influenza kills 30,000 to 40,000 people each year in the United States and causes 10 times as many hospitalizations. A common complication of influenza is bacterial superinfection, which exacerbates morbidity and mortality from the viral illness. Recently, methicillin-resistant (MRSA) has emerged as the dominant pathogen found in bacterial superinfection, with a close second.