Project description:Regulatory T cells (Treg) are a cornerstone of immune regulation. Recent evidence indicates that human Treg show plasticity in specific settings. A subpopulation of Treg expressing CD161, a marker associated with T helper (Th)17 cells, have T effector -like characteristics and are enriched at sites of autoimmune inflammation. Here we used RNAseq to confirm the effector-like signature of CD161+ Treg and demonstrated a shared transcriptional signature between CD161+ Treg and CD161+ conventional T cells (Tconv). Pathway analysis suggested that CD161+ T cells have a migratory phenotype, expressing high levels of CCR9 and integrin α4β7, markers associated with gut homing. In response to all-trans retinoic acid, CD161+ T cells expressed higher levels of CCR9 and integrin α4β7 than CD161- T cells. Our data suggest that blood CD161+ T cells may have adopted gut homing properties upon retinoic acid exposure. In contrast to their peripheral counterparts, CD161+ T cells from the site of autoimmune arthritis have a diminished gut homing phenotype and blunted response to retinoic acid. In health, the TCRβ repertoires of CD161+ and CD161- T cells showed limited overlap whereas there is clear overlap in T cell clones from synovial fluid of autoimmune arthritis patients. We therefore propose that CD161+ and CD161- T cells are largely distinct populations in the healthy immune system but that the inflamed site creates an environment where CD161 levels in T cells can be altered, potentially contributing to disease pathogenesis.
Project description:Human T-cells that express CXCR5 and/or CCR6 provide help to naive B-cells for IgG production. To understand the molecular pathways that are shared or unique to individual B helper T-cell subsets in human peripheral blood, CD4+IL-7R+CD25-/lo helper T-cells were purified according to the expression of CXCR5, CCR6, CXCR3, CD161 and CCR5 as follows: 1) TFH17(CD161-): CXCR5+CXCR6+CXCR3-CD161- 2) Th17: CXCR5-CCR6+CXCR3-, CD161+ or CCR5+ 3) CCR6”SP”: CXCR5-CCR6+CXCR3-CD161-CCR5- RNA-seq was performed with FACS-purified T-cell subsets from 3 healthy individuals.
Project description:Differential gene expression analysis between CD patients and controls to identify the transcriptional signature that defines the inflamed intestinal mucosa in CD.
Project description:Functionality of the accessory gene regulator (agr) quorum sensing system is an important switch promoting either acute or chronic infections, mediated by the notorious opportunistic human and veterinary pathogen Staphylococcus aureus. Spontaneous alterations of the agr system are known to frequently occur in human healthcare-associated S. aureus lineages. However, data on agr integrity and function are sparse regarding other major lineages. Here we report on the agr system functionality and activity level in mecC-carrying methicillin resistant S. aureus (MRSA) of various animal origins (n=33) in Europe together with closely related isolates of human patients (n=12). Whole genome analysis assigned all isolates to four clonal complexes (CC) with distinct agr types (CC599 agr I, CC49 agr II, CC130 agr III and CC1943 agr IV). Different levels of agr functionality were detected by use of different phenotype assays and proteomics for isolates of each CC, including completely non-functional variants. Genomic comparison of the agr I-IV encoding regions revealed that variants of AgrA and AgrC were associated with these phenotype changes, especially among the isolates of pet- and wild animal origin. Since a role in adaptation is most likely when genomic changes occur independently in divergent lineages, agr variation might foster viability and niche adjustment capacities of rare MRSA lineages.
Project description:This SuperSeries is composed of the following subset Series: GSE33374: Expression data from healthy human CD161++CD8aa and CD161++CD8ab T cells GSE33424: Expression data from human cord blood CD161++/CD161+/CD161- CD8+ T cell subsets Refer to individual Series
