Role of PD-L1 and PD-L2 in allergic diseases and asthma.
Asthma is the result of chronic airway inflammation associated predominantly with CD4+ cells, eosinophils, mast cells, and basophils. Several T-cells subsets, including NKT cells, play a critical role in orchestrating the inflammation in the airways predominantly, by secreting interleukin-4 and interleukin-13. Recently, programmed death-1 (PD-1) with its ligands, programmed death ligand B7H1 (PD-L1) and B7DC (PD-L2), was shown to regulate T-cell activation and tolerance. PD-1 has been characterized as a negative regulator of conventional CD4+T cells. In addition, the relative roles of PD-L1 and PD-L2 in regulating the activation and function of T cells have recently been characterized. Recent studies have demonstrated that PD-L1 and PD-L2 have important but opposing roles in modulating and polarizing T-cell functions in airway hyperreactivity. Whereas the severity of asthma is greatly enhanced in absence of PD-L2, PD-L1 deficiency resulted in reduced airway hyperresponsiveness and only minimal inflammation. This observation is partially because of the polarization of NKT cells in PD-L1- and PD-L2-deficient mice. This review will discuss the recent literature regarding the role of PD-L1 and PD-L2 in allergic disease and asthma. Current understanding of the role of PD ligands in allergic asthma gives impetus to the development of novel therapeutic approaches.
Singh
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AK
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, CA 90033, USA.
Stock
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Akbari
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D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology*; D060890:B7-H1 Antigen; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008024:Ligands; D061027:Programmed Cell Death 1 Ligand 2 Protein
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008024:Ligands; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein