B7-H4's role "beyond the tumor"

B7-H4 is a ligand in the B7 costimulatory family, executing suppressive function on the immune system in many diseases, such as cancer, allograft rejection, and autoimmune diseases. The receptor for this molecule has yet to be clarified. The engagement of B7-H4 inhibits proliferation of immune cells by stopping the cell cycle at the G0/G1 phase and leads to apoptosis via the Fas/FasL pathway consequently accelerating tumor progression and alleviating allograft rejection. The pathogenic role of B7-H4 in tumors has been widely established, but few studies have focused on its function in other disorders. Here, we review recent advances in our understanding of B7-H4 biology in disease settings other than tumors and document the beneficial values to treat those diseases by targeting this molecule and related signaling pathways.