Coordinated variation in the immune systems and microbiomes of healthy humans is linked to tonic interferon states.

Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study.

A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment.

Objective: To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.

Design: Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.

Setting: Academic center.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined.

Cell-Specific Transposable Element Gene Expression Analysis Identifies Associations with Systemic Lupus Erythematosus Phenotypes.

There is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to production of type I IFNs and generation of autoantibodies. We profiled cell-sorted RNA-seq data (CD4+ T cells, CD14+ monocytes, CD19+ B cells, and NK cells) from PBMCs of 120 SLE patients and quantified TE expression identifying 27,135 TEs.

Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants.

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes.

Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.

The development of human prenatal adaptive immunity progresses faster than previously appreciated, with the emergence of memory CD4+ T cells alongside regulatory T cells by midgestation. We previously identified a prenatal specific population of promyelocytic leukemia zinc finger-positive (PLZF+) CD4+ T cells with heightened effector potential that were enriched in the developing intestine and accumulated in the cord blood of infants exposed to prenatal inflammation. However, the signals that drive their tissue distribution and effector maturation are unknown.

Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19.

Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find decreased signatures of antigen presentation, T cell recruitment, and viral injury in patients treated with dexamethasone.

Single-Cell Multiomics.

Single-cell RNA sequencing methods have led to improved understanding of the heterogeneity and transcriptomic states present in complex biological systems. Recently, the development of novel single-cell technologies for assaying additional modalities, specifically genomic, epigenomic, proteomic, and spatial data, allows for unprecedented insight into cellular biology. While certain technologies collect multiple measurements from the same cells simultaneously, even when modalities are separately assayed in different cells, we can apply novel computational methods to integrate these data.

Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.

An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined.

Distinct factors associated with short-term and long-term weight loss induced by low-fat or low-carbohydrate diet intervention.

To understand what determines the success of short- and long-term weight loss, we conduct a secondary analysis of dietary, metabolic, and molecular data collected from 609 participants before, during, and after a 1-year weight-loss intervention with either a healthy low-carbohydrate (HLC) or a healthy low-fat (HLF) diet. Through systematic analysis of multidomain datasets, we find that dietary adherence and diet quality, not just caloric restriction, are important for short-term weight loss in both diets. Interestingly, we observe minimal dietary differences between those who succeeded in long-term weight loss and those who did not.

Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets Reveals Genotype-Specific Changes Across Cell Types in Two Brain Regions.

Alzheimer's Disease (AD) is a complex neurodegenerative disease that gravely affects patients and imposes an immense burden on caregivers. Apolipoprotein E4 (APOE4) has been identified as the most common genetic risk factor for AD, yet the molecular mechanisms connecting APOE4 to AD are not well understood. Past transcriptomic analyses in AD have revealed genotype-specific transcriptomic differences; however, these differences have not been explored at a single-cell level.

Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types.

Assessing the health and competence of the immune system is central to evaluating vaccination responses, autoimmune conditions, cancer prognosis, and treatment. With an increasing number of studies examining immune dysregulation, there is a growing need for a curated reference of variation in immune parameters in healthy individuals. We used mass cytometry (CyTOF) to profile blood from 86 humans in response to 15 immune stimuli.

A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.

Animal models are an integral part of the drug development and evaluation process. However, they are unsurprisingly imperfect reflections of humans, and the extent and nature of many immunological differences are unknown. With the rise of targeted and biological therapeutics, it is increasingly important that we understand the molecular differences in the immunological behavior of humans and model organisms.