Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
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:CD38 has emerged as a potential therapeutic target for patients with systemic lupus erythematosus (SLE) but it is not known whether CD38 alters CD4+ T cell function. Using primary human T cells and CD38-sufficient and -deficient Jurkat T cells, we demonstrate that CD38 shifts the T cell lipid profile of gangliosides from GM3 to GM2 by upregulating B4GALNT1 in a Sirtuin 1-dependent manner. Enhanced expression of GM2 causes ER stress by enhancing Ca2+ flux through the PLC_1-IP3 pathway. Interestingly, correction of the calcium overload by an IP3 receptor inhibitor, but not by a store-operated calcium entry (SOCE) inhibitor, improves IL-2 production by CD4+ T cells in SLE. This study demonstrates that CD38 affects calcium homeostasis in CD4+ T cells by controlling cell membrane lipid composition that results in suppressed IL-2 production. CD38 inhibition with biologics or small drugs should be expected to benefit patients with SLE.
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:Stimulation experiments were done with PBMC from SLE or healthy donors treated with CSL362 or isotype control before stimulation with various stimuli including the TLR9 agonist 0.25 μM CpGc; the TLR4 agonist 10 μg/ml LPS; and the TLR3 agonist 10 μg/ml POLY I:C. As well as the SLE specific stimuli SLE immunoglobulin (Ig) + necrotic cell lysates (NCL) to form immune complexes; control healthy donor Ig + NCL; and SLE sera + NCL; or healthy donor sera + NCL to understand the specific effects of pDC depletion on different inducible gene transcripts.
Project description:B cells orchestrate the autoimmune responses in patients with systemic lupus erythematosus (SLE), but broad based B-cell directed therapies only show modest efficacy while attenuating humoral immune responses to vaccines and inducing acquired immunodeficiency. used proteomic and transcriptomic analyses of B cells from patients with SLE and healthy individuals and demonstrated a dominant DDR in SLE B cells.