TY - JOUR TI - CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals AU - Li, Yang AU - Wu, Yan AU - Federzoni, Elena A AU - Wang, Xiaodan AU - Dharmawan, Andre AU - Hu, Xiaoyi AU - Wang, Hui AU - Hawley, Robert J AU - Stevens, Sean AU - Sykes, Megan AU - Yang, Yong-Guang A2 - Yona, Simon A2 - Rath, Satyajit A2 - Discher, Dennis VL - 11 PY - 2022 DA - 2022/12/01 SP - e73677 C1 - eLife 2022;11:e73677 DO - 10.7554/eLife.73677 UR - https://doi.org/10.7554/eLife.73677 AB - Transgenic CD47 overexpression is an encouraging approach to ameliorating xenograft rejection and alloresponses to pluripotent stem cells, and the efficacy correlates with the level of CD47 expression. However, CD47, upon ligation, also transmits signals leading to cell dysfunction or death, raising a concern that overexpressing CD47 could be harmful. Here, we unveiled an alternative source of cell surface CD47. We showed that extracellular vesicles, including exosomes, released from normal or tumor cells overexpressing CD47 (transgenic or native) can induce efficient CD47 cross-dressing on pig or human cells. Like the autogenous CD47, CD47 cross-dressed on cell surfaces is capable of interacting with SIRPĪ± to inhibit phagocytosis. However, ligation of the autogenous, but not cross-dressed, CD47 induced cell death. Thus, CD47 cross-dressing provides an alternative source of cell surface CD47 that may elicit its anti-phagocytic function without transmitting harmful signals to the cells. CD47 cross-dressing also suggests a previously unidentified mechanism for tumor-induced immunosuppression. Our findings should help to further optimize the CD47 transgenic approach that may improve outcomes by minimizing the harmful effects of CD47 overexpression. KW - CD47 KW - macrophages KW - extracellular vesicles KW - exosomes KW - xenotransplantation KW - tumor cells JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -