This SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Disease
View SamplesWe observed separation of COPD patients from control smokers by CD4+ T cell transcriptomics. In contrast to CD4+ T cells, there were no transcript differences in whole blood, CD8+ T cells or CD14+ monocytes.
No associated publication
Specimen part, Disease
View SamplesWe observed no transcripts in the whole blood that distinguishes COPD patients and control smokers. In contrast, T cell directed stimulation of whole blood, resulted in altered transcriptomic response and separated COPD patients from control smokers.
No associated publication
Specimen part, Disease
View SamplesGenomic profiling of bleomycin- and saline-treated mice across 7 timepoints (1, 2, 7, 14, 21, 28, 35 days post treatment) was carried out in C57BL6/J mice to determine the phases of response to bleomycin treatment which correspond to onset of active pulmonary fibrosis.
Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.
Sex, Specimen part, Treatment, Time
View SamplesPolyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sex, Specimen part, Time
View SamplesType I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins and extracellular matrix (ECM) markers were measured in relation to IFN pathway activation status and SSc disease activity. Our results demonstrated a robust overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseline type I IFN gene signature. Anifrolumab administration was associated with significant downregulation of T cellassociated proteins and upregulation of type III collagen degradation marker. Whole-blood and skin microarray results also indicated the inhibition of T cell receptor and ECMrelated transcripts by anifrolumab. In summary, our study demonstrates suppressive effects of anifrolumab on T cell activation and collagen accumulation through which tissue fibrosis may be reduced in SSc patients. The relationship between these peripheral markers and the clinical response to anifrolumab may be examined in larger double-blind, placebo-controlled trials.
Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.
Specimen part, Disease, Disease stage, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
Sex, Age, Race
View SamplesImmune cell infiltration in myositis were by examining microarray expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls.
Genomic signatures characterize leukocyte infiltration in myositis muscles.
Sex, Specimen part, Disease, Disease stage
View SamplesAutoantibodies that arise in autoimmunity can be present years to decades prior to the onset of disease manifestations. This suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which then drives disease pathology in local tissues later in life. To explore the impact of early peripheral immune dysregulation on the progression of Sjgrens Syndrome, we blocked the CD40-CD40L pathway in young female NOD.H-2h4 mice at 4 weeks of age with a single injection of anti-CD40L antibody, and collected total salivary gland at the age of week 8, 16 and 24. RNA was extracted and submitted to transcriptome profiling using Affymetrix microarray.
Autoimmune manifestations in aged mice arise from early-life immune dysregulation.
Treatment
View SamplesThe CD19 positive antibody secreting cells (ASC) in both bone marrow (BM) have the capacity to provide immune memory in addition to cells traditionally considered long-lived, the CD19-negative BM ASC. We performed flow cytometry (FCM) immunophenotyping, fluorescence-activated cell sorting (FACS) for cell subset isolation, ELISpot assays detecting the isotype of antibody secretion as well as antibodies against vaccine derived antigens, and comparative gene expression analyses of CD19- ASC, CD19+ ASC, CD20- B cells, and CD20+ B cells from BM. The findings may aid in the understanding of the differential cell subsets created through vaccination and lead to improved vaccine strategies and production. FACS sorted tissue B cells and antibody secreting cell subset gene expression.
CD19-positive antibody-secreting cells provide immune memory.
Specimen part
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