Disease relevance of PDCD1

• The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus nephritis [1].
• Dysfunction of the PD-1 pathway is thought to result in autoimmune diseases such as rheumatoid arthritis (RA) [2].
• Decreased Risk for Myocardial Infarction and Lower Tumor Necrosis Factor-alpha Levels in Carriers of Variants of the PDCD1 Gene [3].
• Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma [4].
• PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP) [5].

Psychiatry related information on PDCD1

• Programmed cell death, or apoptosis, has been implicated in Alzheimer's disease (AD) [6].
• Programmed cell death plays a pivotal role in several developmental processes of plants and it is involved in the response to environmental stresses and in the defense mechanisms against pathogen attack [7].

High impact information on PDCD1

• Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1 [8].
• A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans [8].
• Programmed cell death: apoptosis and oncogenesis [9].
• Programmed cell death, mitochondria and the plant hypersensitive response [10].
• Programmed cell death (apoptosis) mediated by the cytokine receptor Fas is critical for the removal of autoreactive T cells, the mechanism of immune privilege, and for maintenance of immune-system homeostasis [11].

Chemical compound and disease context of PDCD1

• Programmed cell death (apoptosis) in pancreatic cancers of hamsters after treatment with analogs of both luteinizing hormone-releasing hormone and somatostatin [12].
• Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation [13].
• Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation [14].

Biological context of PDCD1

• A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese [15].
• In contrast, PD-1 signaling inhibits Akt phosphorylation by preventing CD28-mediated activation of phosphatidylinositol 3-kinase (PI3K) [16].
• The ability of PD-1 to suppress PI3K/AKT activation was dependent upon the immunoreceptor tyrosine-based switch motif located in its cytoplasmic tail, adding further importance to this domain in mediating PD-1 signal transduction [16].
• OBJECTIVE: The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families [17].
• PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24 [18].

Anatomical context of PDCD1

• The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice [19].
• OBJECTIVE: Programmed death-1 (PD-1) mediates a negative signal and introduces tolerance for lymphocytes [2].
• Immunohistochemical analysis showed that PD-1 was expressed on infiltrating lymphocytes in salivary gland from 52% of SS patients, and PD-L1 was expressed on ductal and acinar epithelial cells from 68% of SS patients [2].
• The program death 1 (PD-1) receptor and its ligands, PD-1 ligand (PD-L)1 and PD-L2, define a novel regulatory pathway with potential inhibitory effects on T, B, and monocyte responses [20].
• Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells [21].

Associations of PDCD1 with chemical compounds

• PD-1-positive SS salivary lymphocytes expressed IL-10 intracellularly upon PMA/ionomycin stimulation [2].
• Programmed cell death in HUVECs rendered nonadherent by chloroquine was confirmed by the induction of DNA fragmentation in floating cells [22].
• BALB/c mice were divided into three groups: (a) normal mice, (b) adriamycin (ADR) with control immunoglobulin (Ig)G (ADR-IgG), and (c) ADR with anti-PD-1 Ab (ADR-Ab) [23].
• Programmed cell death induced by ceramide [24].
• Programmed cell death in castor bean endosperm is associated with the accumulation and release of a cysteine endopeptidase from ricinosomes [25].

Regulatory relationships of PDCD1

• IL-2 levels induced by costimulation are critical in determining the outcome of the PD-1 engagement [20].
• Programmed cell death (apoptosis) was induced in early time treatments and was accompanied by p53 mRNA induction [26].
• Programmed cell death was shown to be greatly enhanced when cells were growth-arrested prior to EGF treatment [27].

Other interactions of PDCD1

• CONCLUSION: The present study demonstrates a substantial increase in expression of the negative regulator molecules PD-1 and CTLA-4 and the apoptotic signal molecules Fas and FasL in patients with primary SS compared with controls, which corresponded to the immunomorphologic pattern [28].
• OBJECTIVE: Expression of the B7 homolog B7-H1 (PD1-Ligand) has been proposed to enable tumor cells to evade immune surveillance [29].
• CTLA-4 and PD-1 are receptors that negatively regulate T-cell activation [16].
• Under optimal conditions of stimulation, ICOS but not CD28 costimulation can be prevented by PD-1 engagement [20].
• Blocking PD-1 reverted the inhibitory effect of PD-L2, demonstrating involvement of this pathway [30].

Analytical, diagnostic and therapeutic context of PDCD1

• In a case-control study, multiple regression analysis of genotypic data implies that PDCD1 also confers susceptibility to rheumatoid arthritis [31].
• Indirect immunohistochemistry was used to investigate the expression of PD-1 and PD-L1 [2].
• METHODS: Flow cytometry analysis was used to determine expression of PD-1 in SS salivary lymphocytes [2].
• In contrast, B7-H1 blockade suppressed apoptosis of infiltrating PD-1(+) T cells, which led to allograft rejection [32].
• Although purification was limited to resting Treg because TCR ligation induced up-regulation of surface PD-1, this strategy nevertheless represents a valuable step toward more definitive characterization of Treg and their improved purification for therapeutic assessment [21].

References