Disease relevance of Pdcd1lg2

• Differential role of programmed death-ligand 1 and programmed death-ligand 2 in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis [1].
• Treatment of mice with anti-B7-DC mAb at the time of allergen challenge, but not at the time of sensitization, significantly increased their airway hyper-reactivity and eosinophilia [2].
• PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis [3].
• Neither B7-DC or B7RP-1 was augmented after low-dose probiotic or Lactobacillus casei treatment, but B7RP-1 showed increased expression on dendritic cells stimulated with the gram-negative bacterium Escherichia coli [4].
• Involvement of programmed death-ligand 2 (PD-L2) in the development of experimental allergic conjunctivitis in mice [5].

High impact information on Pdcd1lg2

• These results highlight the contrasting in vivo roles of B7-DC and B7-H1 and indicate that B7-DC functions as a tuning molecule, selectively augmenting T helper 1 and CTL responses [6].
• Hepatic tumors grew more quickly in B7-DC KO mice, associated with a decrease in intrahepatic tumor-specific CD8 T cells [6].
• In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses [6].
• This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c(+ )APCs from the airways of ISS-treated mice [7].
• Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor [8].

Biological context of Pdcd1lg2

• In contrast, B7-DC expression was scarcely expressed on dendritic cells in naive mice, but was up-regulated after allergen challenge, although the up-regulation of B7-DC expression on macrophages was minimal [2].
• Competition, transfection, and knockout studies identified the ligand on mouse DC as the costimulatory molecule family member B7-DC [9].
• Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses [10].
• The results showed that MPA not only inhibited the expression of major histocompatibility complex (MHC) class II and costimulatory molecules CD80 and CD86 but upregulated B7-DC expression on mature DC induced by LPS [11].
• DCs matured with TLR agonists and then superactivated through B7-DC exhibit a previously unrecognized phenotype [12].

Anatomical context of Pdcd1lg2

• Moreover, B7DC binds to PD-1(-/-) cells and enhances T cell killing in a PD-1-independent mechanism [13].
• B7-DC is a recently discovered member of the B7 family that binds to PD-1 and is selectively expressed by dendritic cells (DCs) [8].
• Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted [14].
• B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation [15].
• B7-H1 and B7-DC are ligands for PD-1, a receptor implicated in negative regulation of T and B cell functions [16].

Associations of Pdcd1lg2 with chemical compounds

• B7-DC, one of the recently described B7 family members, has the capacity to inhibit T cell responses via engagement of the immunoreceptor tyrosine-based inhibitory motif-containing inhibitory PD-1 receptor as well as enhance responses via an as yet unidentified costimulatory receptor [6].
• Mycophenolic acid upregulates B7-DC expression on dendritic cells, which is associated with impaired allostimulatory capacity of dendritic cells [11].

Regulatory relationships of Pdcd1lg2

• B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism [2].
• In contrast, the B7-DC promoter was induced by IL-4 but not by LPS [17].

Other interactions of Pdcd1lg2

• B6 mice immunized with MOG35-55 developed chronic persistent EAE, and PD-L2 blockade in the chronic phase exacerbated EAE, whereas PD-L1 blockade did not [1].
• Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells [15].
• Additionally, IL-4 increased cell surface expression of B7-DC in both immature and mature DCs [17].
• In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex-peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine [15].
• PD-L1 up-regulation depends on TLR4 and STAT1, whereas PD-L2 expression depends on IL-4R alpha and STAT6 [18].

Analytical, diagnostic and therapeutic context of Pdcd1lg2

• RT-PCR and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in tumor and vicinal muscle tissues of tumor-bearing mice and the expression level was significantly increased if a higher dosage of pSLC was administered [19].
• The parallel signaling events induced in human and mouse DC demonstrate that activation of cells using IgM Ab results in a response governed by a common mechanism and support the hypothesis that B7-DC cross-linking using this Ab may provide beneficial therapeutic immune modulation in human patients similar to those seen in animal models [20].
• CONCLUSION: Activation of DCs with B7-DC XAb ex vivo before adoptive transfer into presensitized mice is sufficient to protect animals completely from inflammatory lung disease induced by subsequent repeated airway exposure to the offending antigen [21].

References