GRaNIE and GRaNPA: inference and evaluation of enhancer-mediated gene regulatory networks.

Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell-type-specific gene regulatory networks (GRN).

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis.

Background: Type I interferons (IFNs) promote the expansion of subsets of CD1c+ conventional dendritic cells (CD1c+ DCs), but the molecular basis of CD1c+ DCs involvement in conditions not associated without elevated type I IFNs remains unclear.

Methods: We analyzed CD1c+ DCs from two cohorts of non-infectious uveitis patients and healthy donors using RNA-sequencing followed by high-dimensional flow cytometry to characterize the CD1c+ DC populations.

Results: We report that the CD1c+ DCs pool from patients with non-infectious uveitis is skewed toward a gene module with the chemokine receptor as the key hub gene.

Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis.

Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here, we performed CyTOF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in juvenile idiopathic arthritis (JIA).

Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.

Objective: This study was undertaken to identify key disease pathways driving conventional dendritic cell (cDC) alterations in systemic sclerosis (SSc).

Methods: Transcriptomic profiling was performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 patients with SSc, including all major disease subtypes. We performed differential expression analysis for the different SSc subtypes and healthy donors to uncover genes dysregulated in SSc.

Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion.

Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of the IFN response in SSc monocytes is sustained by altered epigenetic factors as well as by upregulation of the long non-coding RNA (lncRNA) NRIR.

Angiopoietin-2 Promotes Inflammatory Activation in Monocytes of Systemic Sclerosis Patients.

Angiopoietin-2 (Ang-2), a ligand of the tyrosine kinase receptor Tie2, is essential for vascular development and blood vessel stability and is also involved in monocyte activation. Here, we examined the role of Ang-2 on monocyte activation in patients with systemic sclerosis (SSc). Ang-2 levels were measured in serum and skin of healthy controls (HCs) and SSc patients by ELISA and array profiling, respectively.

Plasmacytoid DCs From Patients With Sjögren's Syndrome Are Transcriptionally Primed for Enhanced Pro-inflammatory Cytokine Production.

Primary Sjögren's syndrome (pSS) is a systemic auto-immune disease typified by dryness of the mouth and eyes. A majority of patients with pSS have a type-I interferon (IFN)-signature, which is defined as the increased expression of IFN-induced genes in circulating immune cells and is associated with increased disease activity. As plasmacytoid dendritic cells (pDC) are the premier type-I IFN-producing cells and are present at the site of inflammation, they are thought to play a significant role in pSS pathogenesis.

The Long Non-coding RNA NRIR Drives IFN-Response in Monocytes: Implication for Systemic Sclerosis.

TLR4 activation initiates a signaling cascade leading to the production of type I IFNs and of the downstream IFN-stimulated genes (ISGs). Recently, a number of IFN-induced long non-coding RNAs (lncRNAs) that feed-back regulate the IFN response have been identified. Dysregulation of this process, collectively known as the "Interferon (IFN) Response," represents a common molecular basis in the development of autoimmune and autoinflammatory disorders.

Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis.

Objective: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease.

Methods: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform.