Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
Project description:In this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy.
Project description:In this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy. RNA-seq was used to asses expression differences in B CD19 Lymphocytes from house dust mite allergic patients and healthy controls.
Project description:In this proof-of-concept study, we piloted a precision endotyping approach focused on DNA methylation biomarkers (CpG methylation) which are regulatory base modifications to DNA that influence cellular immune responses across the life course. The aims of this study were to (a) pilot a precision endotyping approach in a selected group of children from the Rochester prospective cohort who exhibited characteristics of high respiratory infection allergy/asthma prone (IAP) and low vaccine responsiveness (LVR) in early childhood, compared to non-respiratory infection allergy/asthma prone (NIAP) children and (b) assess whether stimulation of PBMCs with stimuli a vaccine adjuvant that activating activates a pattern recognition receptors (PRRs) could re-shape the epigenome.
Project description:The objective of the study was to investigate long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC), to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.
Project description:Despite much promise to overcome drug-resistant infections, clinical studies of bacteriophage anti-bacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains under-studied. Here, we tested the hypotheses that 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages and 2) the activity of the phage recombination machinery (integration / excision / transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results support our hypotheses at the functional protein and gene level. From a human health perspective, are temperate phages part of the problem and not the defenders we wished them to be? These data support the use of lysogenic phages as a therapeutic Trojan Horses.
