Portal de Periódicos da CAPES

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

2014; Rockefeller University Press; Volume: 211; Issue: 5 Linguagem: Inglês

10.1084/jem.20130790

1540-9538

Yanping Xiao, Sanhong Yu, Baogong Zhu, Denis Bedoret, Xia Bu, Loise M. Francisco, Ping Hua, Jonathan S. Duke‐Cohan, Dale T. Umetsu, Arlene H. Sharpe, Rosemarie H. DeKruyff, Gordon J. Freeman,

Immune cells in cancer

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.