Human in vitro-induced IL-17A+ CD8+ T-cells exert pro-inflammatory effects on synovial fibroblasts.

IL-17A+ CD8+ T-cells, termed Tc17 cells, have been identified at sites of inflammation in several immune-mediated inflammatory diseases. However, the biological function of human IL-17A+ CD8+ T-cells is not well characterized, likely due in part to the relative scarcity of these cells. Here, we expanded IL-17A+ CD8+ T-cells from healthy donor PBMC or bulk CD8+ T-cell populations using an in vitro polarization protocol.

Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets.

CD69+CD103+ tissue-resident memory T (T) cells are important drivers of inflammation. To decipher their role in inflammatory arthritis, we apply single-cell, high-dimensional profiling to T cells from the joints of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identify three groups of synovial CD8+CD69+CD103+ T cells: cytotoxic and regulatory T (Treg)-like T cells are present in both PsA and RA, while CD161+CCR6+ type 17-like T cells with a pro-inflammatory cytokine profile (IL-17A+TNFα+IFNγ+) are specifically enriched in PsA.

miR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T-cell activation.

MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways.

Sensitization of knee-innervating sensory neurons by tumor necrosis factor-α-activated fibroblast-like synoviocytes: an in vitro, coculture model of inflammatory pain.

Pain is a principal contributor to the global burden of arthritis with peripheral sensitization being a major cause of arthritis-related pain. Within the knee joint, distal endings of dorsal root ganglion neurons (knee neurons) interact with fibroblast-like synoviocytes (FLS) and the inflammatory mediators they secrete, which are thought to promote peripheral sensitization. Correspondingly, RNA sequencing has demonstrated detectable levels of proinflammatory genes in FLS derived from arthritis patients.

IKZF3/Aiolos Is Associated with but Not Sufficient for the Expression of IL-10 by CD4 T Cells.

The expression of anti-inflammatory IL-10 by CD4 T cells is indispensable for immune homeostasis, as it allows T cells to moderate their effector function. We previously showed that TNF-α blockade during T cell stimulation in CD4 T cell/monocyte cocultures resulted in maintenance of IL-10-producing T cells and identified IKZF3 as a putative regulator of IL-10. In this study, we tested the hypothesis that IKZF3 is a transcriptional regulator of IL-10 using a human CD4 T cell-only culture system.

Presence, function, and regulation of IL-17F-expressing human CD4 T cells.

The pro-inflammatory cytokine IL-17A has been implicated in the immunopathology of inflammatory arthritis. IL-17F bears 50% homology to IL-17A and has recently been suggested to play a role in inflammation. We investigated the induction and cytokine profile of IL-17F CD4 T cells, and how IL-17F may contribute to inflammation.

Anti-TNF treatment negatively regulates human CD4 T-cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype.

TNF-blockade has shown clear therapeutic value in rheumatoid arthritis and other immune-mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF-blockade on CD4 T cell activation, maturation, and proliferation, and assessed whether TNF-inhibitors confer regulatory potential to CD4 T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4 T cells with the anti-TNF monoclonal antibody adalimumab promoted IL-10 expression in CD4 T cells, whilst decreasing cellular activation.

Novel AKT1 mutations associated with cell-cycle abnormalities in gastric carcinoma.

Aim: The aim of this study is to identify the AKT1 gene mutation driven pathogenicity in gastric cancer for Mizo population.

Methods: 50 diffuse-type gastric tumors were analyzed for AKT1 exon 2 and 14 mutations. Cell-cycle aberration was analyzed in the AKT1-mutated samples and the stability of the protein as well as exonic splicing enhancer motifs were examined.

Decolorization of azo dyes (Direct Blue 151 and Direct Red 31) by moderately alkaliphilic bacterial consortium.

Removal of synthetic dyes is one of the main challenges before releasing the wastes discharged by textile industries. Biodegradation of azo dyes by alkaliphilic bacterial consortium is one of the environmental-friendly methods used for the removal of dyes from textile effluents. Hence, this study presents isolation of a bacterial consortium from soil samples of saline environment and its use for the decolorization of azo dyes, Direct Blue 151 (DB 151) and Direct Red 31 (DR 31).