Profiling of Tregs across tissues reveals plasticity in ST2 expression and hierarchies in tissue-specific phenotypes.

Foxp3 regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis and exert tissue-specific functions. In many nonlymphoid tissues, Tregs show enriched expression of the IL-33 receptor ST2. Through comprehensive profiling of murine ST2 and ST2 Tregs, we found that Treg transcriptomes and phenotypes formed a hierarchical relationship across tissues.

Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illness.

Critically ill patients manifest many of the same immune features seen in coronavirus disease 2019 (COVID-19), including both "cytokine storm" and "immune suppression." However, direct comparisons of molecular and cellular profiles between contemporaneously enrolled critically ill patients with and without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited. We sought to identify immune signatures specifically enriched in critically ill patients with COVID-19 compared with patients without COVID-19.

Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations.

Background: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown.

Objective: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe-host interactions modify risk of asthma exacerbation in a season-specific manner.

Methods: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing.

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles.

Endotype of allergic asthma with airway obstruction in urban children.

Background: Black and Hispanic children growing up in disadvantaged urban neighborhoods have the highest rates of asthma and related morbidity in the United States.

Objectives: This study sought to identify specific respiratory phenotypes of health and disease in this population, associations with early life exposures, and molecular patterns of gene expression in nasal epithelial cells that underlie clinical disease.

Methods: The study population consisted of 442 high-risk urban children who had repeated assessments of wheezing, allergen-specific IgE, and lung function through 10 years of age.

Autoreactive CD8+ T cell exhaustion distinguishes subjects with slow type 1 diabetes progression.

Although most patients with type 1 diabetes (T1D) retain some functional insulin-producing islet β cells at the time of diagnosis, the rate of further β cell loss varies across individuals. It is not clear what drives this differential progression rate. CD8+ T cells have been implicated in the autoimmune destruction of β cells.

A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract.

The immune system of the cervicovaginal tract (CVT) must balance immunosurveillance and active immunity against pathogens with maintenance of tolerance to resident microbiota and to fetal and partner antigens for reproductive purposes. Thus, we predicted that CVT immunity is characterized by distinctive features compared to blood and other tissue compartments. Indeed, we found that CVT CD8+ T-cells had unique transcriptional profiles, particularly in their cytokine signature, compared to that reported for CD8+ T-cells in other tissue sites.

Infants with evolving bronchopulmonary dysplasia demonstrate monocyte-specific expression of IL-1 in tracheal aspirates.

Bronchopulmonary dysplasia (BPD) remains a devastating consequence of prematurity. Repeated inflammatory insults worsen lung injury, but there are no predictors for BPD-related respiratory outcomes or targeted therapies. We sought to understand inflammatory mechanisms in evolving BPD through molecular characterization of monocytes in tracheal aspirates from infants at risk for developing BPD.

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation.

Elevated T cell levels in peripheral blood predict poor clinical response following rituximab treatment in new-onset type 1 diabetes.

Biologic treatment of type 1 diabetes (T1D) with agents including anti-CD3 (otelixizumab and teplizumab), anti-CD20 (rituximab), LFA3Ig (alafacept), and CTLA4Ig (abatacept) results in transient stabilization of insulin C-peptide, a surrogate for endogenous insulin secretion. With the goal of inducing more robust immune tolerance, we used systems biology approaches to elucidate mechanisms associated with C-peptide stabilization in clinical trial blood samples from new-onset T1D subjects treated with the B cell-depleting drug, rituximab. RNA sequencing (RNA-seq) analysis of whole-blood samples from this trial revealed a transient increase in heterogeneous T cell populations, which were associated with decreased pharmacodynamic activity of rituximab, increased proliferative responses to islet antigens, and more rapid C-peptide loss.

A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification.

The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB).

Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma.

Background: Childhood asthma in inner-city populations is a major public health burden, and understanding early-life immune mechanisms that promote asthma onset is key to disease prevention. Children with asthma demonstrate a high prevalence of aeroallergen sensitization and T2-type inflammation; however, the early-life immune events that lead to T2 skewing and disease development are unknown.

Objective: We sought to use RNA sequencing of PBMCs collected at age 2 years to determine networks of immune responses that occur in children with allergy and asthma.

Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.

Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P.

A curated transcriptome dataset collection to investigate the functional programming of human hematopoietic cells in early life.

Compendia of large-scale datasets made available in public repositories provide an opportunity to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to research investigators for interpretation. Here we make available a collection of transcriptome datasets to investigate the functional programming of human hematopoietic cells in early life.

A curated transcriptome dataset collection to investigate the development and differentiation of the human placenta and its associated pathologies.

Compendia of large-scale datasets made available in public repositories provide a precious opportunity to discover new biomedical phenomena and to fill gaps in our current knowledge. In order to foster novel insights it is necessary to ensure that these data are made readily accessible to research investigators in an interpretable format. Here we make a curated, public, collection of transcriptome datasets relevant to human placenta biology available for further analysis and interpretation via an interactive data browsing interface.

A curated compendium of monocyte transcriptome datasets of relevance to human monocyte immunobiology research.

Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. However, resources that can serve as an interface between biomedical researchers and such vast and heterogeneous dataset collections are needed in order to fulfill this potential.

A compendium of monocyte transcriptome datasets to foster biomedical knowledge discovery.

Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. However, resources that can serve as an interface between biomedical researchers and such vast and heterogeneous dataset collections are needed in order to fulfill this potential.

A curated transcriptome dataset collection to investigate the immunobiology of HIV infection.

Compendia of large-scale datasets available in public repositories provide an opportunity to identify and fill current gaps in biomedical knowledge. But first, these data need to be readily accessible to research investigators for interpretation. Here, we make available a collection of transcriptome datasets relevant to HIV infection.

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response.

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination.

An interactive web application for the dissemination of human systems immunology data.

Background: Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation.

Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures.

Objective: The role of interferon-α (IFNα) in the pathogenesis of systemic lupus erythematosus (SLE) is strongly supported by gene expression studies. The aim of this study was to improve characterization of the blood IFN signature in adult SLE patients.

Methods: Consecutive patients were enrolled and followed up prospectively.

Molecular signatures of antibody responses derived from a systems biology study of five human vaccines.

Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus.