RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance
Umetsu, Dale T.
DeKruyff, Rosemarie H.
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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.
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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454707
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