ABSTRACT: Differential gene expression profiling in CD4+ T cells and CD19+ B cells between rituximab-treated complete remission (CR) and incomplete remission (IR) pemphigus patients
Project description:To understand the molecular and immunological mechanisms of remission in pemphigus patients. Remission was evaluated 5 years after rituximab onset. PBMC were purified from pemphigus whole blood patients. CD4+ T cells and CD19+ B cells were isolated by flow cytometry. Genes differentially regulated between CR and IR both in CD4+ and CD19+ cells were identified by transcriptomic approach (whole human genome).
Project description:Pemphigus, a rare autoimmune bullous disease mediated by anti-desmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area, requiring long-term maintenance systemic therapy. We demonstrate the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from pemphigus patients. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T-cell receptor-mediated signaling. Regulatory T cells (Tregs) are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-β stimulation. Lastly, Intralesional corticosteroid injection improved chronic blisters and reduce skin TLSs in patients with pemphigus. This study concludes that skin TLSs are associated with the persistence of chronically recurrent blisters in pemphigus patients, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.
Project description:1) Transcriptional profiles of highly purified (≥ 98%) PB CD8+ T-cells from newly diagnosed AML patients (pre-treatment) were compared to age-matched healthy controls and transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment and upon recovery following induction chemotherapy (paired samples). 2) Transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment (PRE) and upon recovery following induction chemotherapy (POST) (paired samples).
2018-12-26 | GSE109179 | GEO
Project description:CD4+ tissue-resident memory T cells in pemphigus lesions
Project description:Identify biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) using gene expression microarrays. 42 samples from 13 controls, 14 active patients, 9 patients in clinical remission with medication (CRM), and 6 patients in clinical remission without medication (CR). All patients had polyarticular JIA.
Project description:Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. The rice variety IR-64 was germinated and allowed to grow for 5 d at 37 C and then transferred to Hewitt solution for growth. After 10 d of growth, seedlings of uniform size and growth were treated with 100 µM of Cr (VI), As (V), Cd, and Pb under standard physiological conditions of 16 h light (115 μmol m−2 s−1) and 8 h dark photoperiod at 25 ± 2 C for 24 h. Total RNA was extracted from the treated rice roots and microarray was performed using one-cycle target labeling and control reagents (Affymetrix platform).
Project description:Interventions: Experimental group:CART cells
Primary outcome(s): Safety and objective remission rate of CAR-T targeted therapy in patients with advanced urinary tract tumors (complete remission [CR] + partial remission [PR]
Study Design: Single arm
Project description:Gene expression profile at single cell level of bone marrow (BM) T cells and hematopoietic stem and progenitor cells (HSPCs) of acute myeloid leukemia patients post allogeneic stem cell transplantation (alloSCT) of patients in complete remission (CR) and relapse (REL).
Project description:B cell identity and function is dependent on the proteins residing in the B cell surfaceome and their respective nanoscale organization. Here we show that CD20 is a gatekeeper for B cell identity and function due to its control of the functional nanoscale organization of receptors within the B surfaceome and the resting state of B lymphocytes. CRISPR/Cas-based ablation of CD20 in Ramos B cells revealed that IgM class B cell antigen receptor (IgM-BCR) and the co-receptor CD19 are functionally interlinked in the absence of CD20. The resulting IgM-BCR/CD19 signalling synapse leads to transient B cell activation and the loss of B cell identity. Re-expression of CD20 involving an aptamer-controlled riboswitch restores resting-state B cell nanoscale organization and function. Treatment of naive human B cells with the anti-CD20 antibody Rituximab leads to transient B cell activation and formation of transiently activated IgM-BCR/CD19 signalling synapses providing new insights into the molecular mode of action of Rituximab. The loss of B cell identity due to CD20-deficiency is accompanied by a PAX5 to BLIMP-1 transcriptional switch and increased plasma cell development. This cellular B cell differentiation towards plasma B cells is mechanistically accompanied by a metabolic shift towards oxidative phosphorylation.
Project description:The aim of this study was to identify differential gene expression in lung T cell subsets upon germline Serpinb1a ablation. CD8-CD19- lymphocytes enriched by negative selection from digested lungs of naïve, 9-12 week old wild-type 129S6 mice or Serpinb1a homozygous null mice were FACS sorted into CD4+ CCR6+ effector/ memory T cells, gd T cells, or CD4+ CD25hiCD127low regulatory T cells. FACS sorted cells were collected into RLT buffer (Qiagen) directly, lysed, and total mRNA was isolated using Quiagen's RNeasy mini kit. Wild-type vs. Serpinb1a-/- gd+ T cells, CD4+ CCR6+ effector/ memory T cells, or CD4+ CD25hiCD127low regulatory T cells
