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:Bulk RNAsequencing of CD8+ 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: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: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:A better understanding of the mechanisms involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR5- CXCR3+ PD1hi CD4+ T cell ‘helper’ population distinct from follicular helper T cells (Tfh) and expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNand high levels of IL10. Additionally, they accumulate high amounts of mitochondrial ROS (mtROS) as the result of reverse electron transport (RET) fueled by succinate. These cells provide potent help to B cells through the synergistic effect of IL10 and succinate. Cells with similar phenotype and function are generated in vitro upon priming naïve CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)-activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE.
Project description:A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell ‘helper’ population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses 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: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.