RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance

We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also binds to repulsive guidance molecule b (RGMb), which was originally identified in the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2 and BMP-2/4 bind to distinct sites on RGMb. Normal restin...

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Vydáno v:	The Journal of experimental medicine Ročník 211; číslo 5; s. 943
Hlavní autoři:	Xiao, Yanping, Yu, Sanhong, Zhu, Baogong, Bedoret, Denis, Bu, Xia, Francisco, Loise M, Hua, Ping, Duke-Cohan, Jonathan S, Umetsu, Dale T, Sharpe, Arlene H, DeKruyff, Rosemarie H, Freeman, Gordon J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 05.05.2014
Témata:	Animals Bone Morphogenetic Protein 2 - metabolism Cell Line, Tumor Epithelial Cells - metabolism Humans Immune Tolerance - immunology Lung - immunology Lung - metabolism Macrophages, Alveolar - metabolism Mice Nerve Tissue Proteins - immunology Nerve Tissue Proteins - metabolism Programmed Cell Death 1 Ligand 2 Protein - immunology Programmed Cell Death 1 Ligand 2 Protein - metabolism Protein Binding
ISSN:	1540-9538, 1540-9538
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Popis
Shrnutí:	We report that programmed death ligand 2 (PD-L2), a known ligand of PD-1, also binds to repulsive guidance molecule b (RGMb), which was originally identified in the nervous system as a co-receptor for bone morphogenetic proteins (BMPs). PD-L2 and BMP-2/4 bind to distinct sites on RGMb. Normal resting lung interstitial macrophages and alveolar epithelial cells express high levels of RGMb mRNA, whereas lung dendritic cells express PD-L2. Blockade of the RGMb-PD-L2 interaction markedly impaired the development of respiratory tolerance by interfering with the initial T cell expansion required for respiratory tolerance. Experiments with PD-L2-deficient mice showed that PD-L2 expression on non-T cells was critical for respiratory tolerance, but expression on T cells was not required. Because PD-L2 binds to both PD-1, which inhibits antitumor immunity, and to RGMb, which regulates respiratory immunity, targeting the PD-L2 pathway has therapeutic potential for asthma, cancer, and other immune-mediated disorders. Understanding this pathway may provide insights into how to optimally modulate the PD-1 pathway in cancer immunotherapy while minimizing adverse events.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1540-9538 1540-9538
DOI:	10.1084/jem.20130790