Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D03301 (PDL)
 658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4(+)CD25(+) regulatory T cells (Treg) but not a direct effect on effector T cells. In this report, we further investigated the effects of E2 on APC and Treg function. We found that E2 treatment in vivo strongly reduced recovery of APC from the peritoneal cavity and inhibited induction of the inflammatory cytokines interleukin (IL)-12 and interferon-gamma but enhanced secretion of IL-10. Moreover, E2-conditioned bone marrow-derived dendritic cells (BM-DC) could both enhance Treg activity and directly inhibit responder T cells in the absence of Treg cells. We examined whether this E2-induced inhibitory activity of BM-DC might involve costimulation through the recently described PD-1 pathway. Both E2 and pregnancy markedly enhanced PD-1 expression in several types of APC, including macrophages, B cells, and especially dendritic cells (DC). Similarly to E2-induced enhancement of FoxP3 expression and experimental autoimmune encephalomyelitis protection, E2-induced enhancement of PD-1(+) cells was also mediated through estrogen receptor alpha (Esr1) in DC and macrophages but not in B cells. Based on antibody inhibition studies, PD-1 interaction with its ligands, PDL-1 and especially PDL-2, could mediate either positive or negative regulatory signaling in both mature and immature E2-conditioned DC, depending, respectively, on a relatively high (10:1) or low (1:1) ratio of T cells:BM-DC. These novel findings indicate that E2-induced immunomodulation is mediated in part through potentiation in BM-DC of the PD-1 costimulatory pathway.
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PMID:Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of Treg cells, and enhanced expression of the PD-1 costimulatory pathway. 1667 26

Bone marrow mesenchymal stem cells (MSCs) demonstrate functions of immunologic regulation. However, little is known about the role of interferon-gamma (IFN-gamma) on MSCs and whether MSCs alone can prevent allograft rejection. We purified MSCs, which were or were not treated with IFN-gamma, to act as regulatory cells in mixed lymphocyte reactions. We measured their expression of PDL-1, MHC-I, MHC-II, CD40, CD54, and CD86. The MSCs stained with carboxyfluorescein diacetate-succinimidyl ester were used to detect homing in vivo. The MSCs were injected into an orthotopic liver transplantation model. The result suggested that IFN-gamma enhances expression of PDL-1, MHC-I, MHC-II, and CD54 and boosts immunosuppressive ability in vivo. The MSCs demonstrated homing to the liver, alleviating acute immunologic rejection of an hepatic graft in rats. We conclude that IFN-gamma may enhance the immunosuppressive function of MSCs to protect liver allografts in rats from acute immunologic rejection.
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PMID:Immunosuppressive function of bone marrow mesenchymal stem cells on acute rejection of liver allografts in rats. 1924 67