Abstract:This study aimed to test the functional effects of the PD1.3 single nucleotide polymorphism (SNP) (rs11568821), which were proposed based on its association to systemic lupus erythematosus (SLE) susceptibility and in electrophoretic mobility shift assays (EMSA) results. We analysed transcriptional effects of the PD1.3 locus by enhancer reporter assays. Results were against the hypothesis that the PD1.3 locus acts as enhancer in transcriptional regulation of PDCD1. In addition, they excluded a differential effe… Show more
“…PDCD1 binds to its ligands, including PD‐L1 and PD‐L2, then recruits protein tyrosine kinases, which produces a coactivated effect that is necessary for inhibition of the dysimmunity reaction. A recent study reported that the anomalous connection of RUNX1 and the PDCD1 single nucleotide polymorphism PD1.3 is essential to the pathogenesis of systemic lupus erythematosus (SLE) 21 . We did not find significant difference in mRNA expression of PDCD1 between the psoriasis and control groups.…”
Section: Discussioncontrasting
confidence: 76%
“…A recent study reported that the anomalous connection of RUNX1 and the PDCD1 single nucleotide polymorphism PD1.3 is essential to the pathogenesis of systemic lupus erythematosus (SLE). 21 We did not find significant difference in mRNA expression of PDCD1 between the psoriasis and control groups.…”
Expression of the critical transcription factor RUNX1, which regulates CD34+ cell development and differentiation, was abnormal, and augmentation of these expression levels might induce dysfunction of marrow haematopoietic stem cells and the haematopoietic microenvironment and be involved in the progression of psoriasis.
“…PDCD1 binds to its ligands, including PD‐L1 and PD‐L2, then recruits protein tyrosine kinases, which produces a coactivated effect that is necessary for inhibition of the dysimmunity reaction. A recent study reported that the anomalous connection of RUNX1 and the PDCD1 single nucleotide polymorphism PD1.3 is essential to the pathogenesis of systemic lupus erythematosus (SLE) 21 . We did not find significant difference in mRNA expression of PDCD1 between the psoriasis and control groups.…”
Section: Discussioncontrasting
confidence: 76%
“…A recent study reported that the anomalous connection of RUNX1 and the PDCD1 single nucleotide polymorphism PD1.3 is essential to the pathogenesis of systemic lupus erythematosus (SLE). 21 We did not find significant difference in mRNA expression of PDCD1 between the psoriasis and control groups.…”
Expression of the critical transcription factor RUNX1, which regulates CD34+ cell development and differentiation, was abnormal, and augmentation of these expression levels might induce dysfunction of marrow haematopoietic stem cells and the haematopoietic microenvironment and be involved in the progression of psoriasis.
“…Based on their model, patients who carry this allele may have a lower expression of PD-1 molecule in activated lymphocytes, and could have a better response to IFN-a stimulation. However other authors, using a luciferase reporter assays, showed that the two alleles of PD-1.3 have similar effects on reporter gene transcription [39]. In spite of the possible implication of this polymorphism in the regulation of protein expression, this study clearly showed that PD-1.3 modulated the outcome to treatment for HCV infection treatment.…”
“…The mechanistic link between PD-1 or PD-L1 expression and the pathogenesis of human SLE is not well understood. Polymorphisms in the PD-1 gene are associated with SLE susceptibility in some populations of adults and children1112131415. However, PD-L1 gene polymorphisms were not associated with SLE1617.…”
Monocytes in patients with systemic lupus erythematosus (SLE) are hyperstimulatory for T lymphocytes. We previously found that the normal program for expression of a negative costimulatory molecule programmed death ligand-1 (PD-L1) is defective in SLE patients with active disease. Here, we investigated the mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1 expression on cultured SLE monocytes correlated with TNF-α expression. Exogenous TNF-α restored PD-L1 expression on lupus monocytes. Conversely, TGF-β inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by opposing actions of TNF-α and TGF-β. As PD-L1 functions to fine tune lymphocyte activation, dysregulation of cytokines resulting in reduced expression could lead to loss of peripheral T cell tolerance.
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