Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA605250 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11036020_1.fastq.gz | Fastqsanger.gz | |||
| SRR11036020_2.fastq.gz | Fastqsanger.gz | |||
| SRR11036021_1.fastq.gz | Fastqsanger.gz | |||
| SRR11036021_2.fastq.gz | Fastqsanger.gz | |||
| SRR11036022_1.fastq.gz | Fastqsanger.gz |
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Project description:The presence of the PTPN22 risk variant (1858T) is associated to several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk variant on T cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve CD4+ T cells carrying two PTPN22 risk alleles overexpress a limited number of genes including CFLAR and 4-1BB important for cytotoxic T cell differentiation. Moreover, an increased number of cytotoxic EOMES+ CD4+ T cells were observed in PTPN22 risk allele carriers, which negatively correlated with a decreased number of naïve T cells in older individuals. No difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg) was observed in PTPN22 risk allele carriers and Treg suppressive capacity was not altered. Finally, in synovial fluids of RA patients, an accumulation of EOMES+ CD4+ T cells was observed with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, our data provide a novel mechanism of action of PTPN22 risk variant on CD4+ T-cell differentiation and identify EOMES+ CD4+ T cell as a relevant T cell subset in RA.
2018-02-27 | GSE94859 | GEO
Project description:Major autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis, rheumatoid arthritis and Graves’ disease display a striking female bias, with a female-to-male incidence ratio ranging up to 9:1 in SLE. Sex hormones contribute to protection of males from autoimmunity, but precise molecular mechanisms of such protection are poorly understood. Here, we find that Androgen Receptor (AR), a nuclear receptor regulating a plethora of genes, is active in T cells during development and regulates directly genes involved in T cell activation or indirectly through regulation of other transcription factors. A gene encoding a phosphatase Ptpn22, a negative regulator of T cell receptor signaling, was found to be dependent of the presence of androgen receptor (AR) in males. Castration or deletion of AR reduced expression of Ptpn22. In a mouse model of Systemic Lupus Erythematosus (SLE), Ptpn22 deletion led to the loss of sexual dimorphism. Moreover, analysis of the regulatory regions of Ptpn22 gene revealed a highly conserved sequence that was necessary for upregulation of the gene’s expression by androgens. Mutation of this sequence in Non-Obese Diabetic (NOD) mice led to enhanced ability of T cells to cause Type 1 diabetes. Thus, PTPN22 is likely to participate in disease pathogenesis making it and other AR-regulated genes fair targets for therapeutic interventions in major autoimmune diseases.
2023-06-07 | GSE234134 | GEO
Project description:Pharmacogenomics of Rheumatoid Arthritis Therapy
| PRJNA294478 | ENA
Project description:Differential DNA methylation in Rheumatoid arthritis
| PRJNA183708 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature