Epitopes described in "PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions."

Article Authors:O Akbari; P Stock; A K Singh; V Lombardi; W-L Lee; G J Freeman; A H Sharpe; D T Umetsu; R H Dekruyff
Article Title:PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions.
Reference Detail
Reference ID:1026248
Abstract:Interactions of the inhibitory receptor programmed death-1 (PD-1) with its ligands, programmed death ligand (PD-L)1 and PD-L2, regulate T-cell activation and tolerance. In this study, we investigated the role of PD-L1 and PD-L2 in regulating invariant natural killer T (iNKT)-cell-mediated airway hyperreactivity (AHR) in a murine model of asthma. We found that the severity of AHR and airway inflammation is significantly greater in PD-L2(-/-) mice compared with wild-type mice after either ovalbumin (OVA) sensitization and challenge or administration of alpha-galactosylceramide (alpha-GalCer). iNKT cells from PD-L2(-/-) mice produced significantly more interleukin (IL)-4 than iNKT cells from control mice. Moreover, blockade of PD-L2 interactions of wild-type iNKT cells in vitro with monoclonal antibodies (mAbs) resulted in significantly enhanced levels of IL-4 production. In contrast, PD-L1(-/-) mice showed significantly reduced AHR and enhanced production of interferon-gamma (IFN-gamma) by iNKT cells. iNKT-deficient Jalpha18(-/-) mice reconstituted with iNKT cells from PD-L2(-/-) mice developed high levels of AHR, whereas mice reconstituted with iNKT cells from PD-L1(-/-) mice developed lower levels of AHR compared with control. As PD-L2 is not expressed on iNKT cells but rather is expressed on lung dendritic cells (DCs), in which its expression is upregulated by allergen challenge or IL-4, these findings suggest an important role of PD-L2 on lung DCs in modulating asthma pathogenesis. These studies also indicate that PD-L1 and PD-L2 have important but opposing roles in the regulation of AHR and iNKT-cell-mediated activation.
Affiliations:Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. akbari@usc.edu.
Reference Type:Literature
PubMed ID:19741598
Journal:Mucosal Immunol
Journal Volume:3
Article Pages:81-91
Journal ISSN:1935-3456
Article Chemical List:Antibodies, Blocking;Antigens, CD274;Antigens, CD80;Cd274 protein, mouse;Galactosylceramides;Membrane Glycoproteins;Pdcd1lg2 protein, mouse;Peptides;Programmed Cell Death 1 Ligand 2 Protein;Interleukin-4;Interferon-gamma;Ovalbumin
Article MeSH List:Animals; Antibodies, Blocking; Antigens, CD274; Antigens, CD80(genetics; immunology; metabolism); Asthma(genetics; immunology; pathology); Cells, Cultured; Dendritic Cells(immunology; metabolism; pathology); Female; Galactosylceramides(immunology); Interferon-gamma(biosynthesis; genetics); Interleukin-4(biosynthesis; genetics); Lung(pathology); Membrane Glycoproteins(genetics; immunology; metabolism); Mice; Mice, Inbred BALB C; Mice, Knockout; Natural Killer T-Cells(immunology; metabolism; pathology); Ovalbumin(immunology); Peptides(genetics; immunology; metabolism); Programmed Cell Death 1 Ligand 2 Protein
Curation Last Updated:2016-05-11 20:12:02