Project description:Bulk RNAsequencing of CD4+ T-cells in SLE patients with (SLE-P) and without (SLE-NP) subclinical atherosclerotic plaques in carotid and femoral arteries, scanned by vascular ultrasound.
Project description:To investigate the lncRNAs expression profiling in CD4+ T cells of systemic lupus erythematosus (SLE) patients, we have employed “Agilent Human lncRNA 4*180K microarray” as a discovery platform to identify lncRNAs and mRNAs expression signatures in CD4+ T cells between SLE patients and normal controls. CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of peripheral blood in SLE patients and normal controls, respectively.
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects 20-150 out of 100,000 people globally. Reactive oxygen species (ROS) generation from mitochondrial dysfunction contributes to risk for SLE and autoimmune states and are potential targets for the treatment of autoimmunity. HRES-1/Rab4 (Rab4A) is a GTPase linked to mitochondrial oxidative stress and activation of the mechanistic target of rapamycin (mTOR), and has been linked to SLE pathogenesis. Here, RNA-sequencing (RNA-seq) was used to examine the expression of different classes of splenocytes (CD4+, CD8+, CD19+) from the lupus-prone SLE1.2.3. triple-congenic (B6.TC) mouse, as well as Rab4AQ72L mutant mice (which exhibits constitutive overexpression of Rab4a), and mice with CD4 T cell-specific deletion of Rab4A (KO).
Project description:ATAC-seq analysis of CD4 T cell populations obtained in blood of systemic lupus erythematosus (SLE) patients. The overall goal of this study was to determine chromatin accessibility profiles in Tfh cells and CXCR3+ PD1hi CD4+ T cells obtained from blood of SLE donors.
Project description:Male patients with systemic lupus erythematosus (SLE) experience severe disease compared to female patients, despite the disease being more prevalent in females. For the time, we compared genome-wide differential methylation in CD4+ T cells between male (n=12) and female (n=10) SLE patients.
Project description:Expansion of different CD4+ CXCR5+ and CXCR5- memory T helper cells has been reported in human systemic lupus erythematosus (SLE) blood. To understand their complexity, we profiled blood CD4+ T cells from heathy donors (HD) and pediatric SLE patients at the single cell level and identified naïve, memory, regulatory (Treg) and proliferative clusters, as well as a cluster defined by high expression of interferon-stimulated genes (ISGs). Within the memory compartment, we mapped follicular (Tfh) and peripheral (Tph and Th10) helper cells and confirmed their expansion in patients with lupus nephritis (LN) and/or high disease activity. Cytotoxic programs mapped to effector memory T cells re-expressing CD45RA (TEMRA), as well as to two memory subclusters, one of which overlapped with Th10 cells. Importantly, we identified an expansion of dysfunctional Tregs in patients with LN, and an upregulation of TLR5 and FCRL3 in naïve SLE Tregs, potentially linking their dysfunction with mucosal microbial dysbiosis. Our studies shed light into CD4+ T cell subsets that may contribute to dysfunctional B cell help and T cell suppression in SLE.
Project description:Expansion of different CD4+ CXCR5+ and CXCR5- memory T helper cells has been reported in human systemic lupus erythematosus (SLE) blood. To understand their complexity, we profiled blood CD4+ T cells from heathy donors (HD) and pediatric SLE patients at the single cell level and identified naïve, memory, regulatory (Treg) and proliferative clusters, as well as a cluster defined by high expression of interferon-stimulated genes (ISGs). Within the memory compartment, we mapped follicular (Tfh) and peripheral (Tph and Th10) helper cells and confirmed their expansion in patients with lupus nephritis (LN) and/or high disease activity. Cytotoxic programs mapped to effector memory T cells re-expressing CD45RA (TEMRA), as well as to two memory subclusters, one of which overlapped with Th10 cells. Importantly, we identified an expansion of dysfunctional Tregs in patients with LN, and an upregulation of TLR5 and FCRL3 in naïve SLE Tregs, potentially linking their dysfunction with mucosal microbial dysbiosis. Our studies shed light into CD4+ T cell subsets that may contribute to dysfunctional B cell help and T cell suppression in SLE.
Project description:We screened SLE monocytes from 19 SLE patients and selected 4 that induced CD4+ T cell proliferation in vitro and 4 that did not. CFSE labeled CD4-T cells (105) were incubated with SLE monocytes (2 x 104). Cells were harvested at 6 hours for RNA extraction. We screened SLE monocytes from 19 SLE patients and selected 4 that induced CD4+ T cell proliferation in vitro and 4 that did not. CFSE labeled CD4-T cells (105) were incubated with SLE monocytes (2 x 104). Cells were harvested at 6 hours for RNA extraction.
Project description:T cell abnormalities are well-known features of patients with systemic lupus erythematosus (SLE). The role of CD4 and CD8 T lymphocytes, however, remains poorly understood with data suggesting both protective and deleterious roles. This project aimed to identify a cell-specific transcriptional signature in patients with SLE that could be used as a prognostic disease marker. The overall objective is to correlate the clinical presentation with specific RNA signatures to determine if there are signatures that correlate with disease outcome