dc.contributor.author | Xiao, Yanping | en_US |
dc.contributor.author | Yu, Sanhong | en_US |
dc.contributor.author | Zhu, Baogong | en_US |
dc.contributor.author | Bedoret, Denis | en_US |
dc.contributor.author | Bu, Xia | en_US |
dc.contributor.author | Francisco, Loise M. | en_US |
dc.contributor.author | Hua, Ping | en_US |
dc.contributor.author | Duke-Cohan, Jonathan S. | en_US |
dc.contributor.author | Umetsu, Dale T. | en_US |
dc.contributor.author | Sharpe, Arlene H. | en_US |
dc.contributor.author | DeKruyff, Rosemarie H. | en_US |
dc.contributor.author | Freeman, Gordon J. | en_US |
dc.date.accessioned | 2014-12-02T21:28:15Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Xiao, Y., S. Yu, B. Zhu, D. Bedoret, X. Bu, L. M. Francisco, P. Hua, et al. 2014. “RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.” The Journal of Experimental Medicine 211 (5): 943-959. doi:10.1084/jem.20130790. http://dx.doi.org/10.1084/jem.20130790. | en |
dc.identifier.issn | 0022-1007 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454707 | |
dc.description.abstract | 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. | en |
dc.language.iso | en_US | en |
dc.publisher | The Rockefeller University Press | en |
dc.relation.isversionof | doi:10.1084/jem.20130790 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010901/pdf/ | en |
dash.license | LAA | en_US |
dc.title | RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | The Journal of Experimental Medicine | en |
dash.depositing.author | Xiao, Yanping | en_US |
dc.date.available | 2014-12-02T21:28:15Z | |
dc.identifier.doi | 10.1084/jem.20130790 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Hua, Ping | |
dash.contributor.affiliated | Xiao, Yanping | |
dash.contributor.affiliated | Bedoret, Denis | |
dash.contributor.affiliated | Yu, Sanhong | |
dash.contributor.affiliated | Francisco, Loise | |
dash.contributor.affiliated | Bu, Xia | |
dash.contributor.affiliated | Sharpe, Arlene | |
dash.contributor.affiliated | Duke-Cohan, Jonathan | |
dash.contributor.affiliated | Freeman, Gordon | |