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dc.contributor.authorXiao, Yanpingen_US
dc.contributor.authorYu, Sanhongen_US
dc.contributor.authorZhu, Baogongen_US
dc.contributor.authorBedoret, Denisen_US
dc.contributor.authorBu, Xiaen_US
dc.contributor.authorFrancisco, Loise M.en_US
dc.contributor.authorHua, Pingen_US
dc.contributor.authorDuke-Cohan, Jonathan S.en_US
dc.contributor.authorUmetsu, Dale T.en_US
dc.contributor.authorSharpe, Arlene H.en_US
dc.contributor.authorDeKruyff, Rosemarie H.en_US
dc.contributor.authorFreeman, Gordon J.en_US
dc.date.accessioned2014-12-02T21:28:15Z
dc.date.issued2014en_US
dc.identifier.citationXiao, 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.issn0022-1007en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454707
dc.description.abstractWe 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.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1084/jem.20130790en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010901/pdf/en
dash.licenseLAAen_US
dc.titleRGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory toleranceen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Experimental Medicineen
dash.depositing.authorXiao, Yanpingen_US
dc.date.available2014-12-02T21:28:15Z
dc.identifier.doi10.1084/jem.20130790*
dash.authorsorderedfalse
dash.contributor.affiliatedHua, Ping
dash.contributor.affiliatedXiao, Yanping
dash.contributor.affiliatedBedoret, Denis
dash.contributor.affiliatedYu, Sanhong
dash.contributor.affiliatedFrancisco, Loise
dash.contributor.affiliatedBu, Xia
dash.contributor.affiliatedSharpe, Arlene
dash.contributor.affiliatedFreeman, Gordon
dash.contributor.affiliatedDuke-Cohan, Jonathan


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