Donor SIRPα binding to recipient CD47 is required for triggering the innate alloresponse. Donor SIRPα binding to recipient CD47 is required for triggering.

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Donor SIRPα binding to recipient CD47 is required for triggering the innate alloresponse. Donor SIRPα binding to recipient CD47 is required for triggering the innate alloresponse. (A) NOD grafts were transplanted to BRG mice that received either hCD47-Fc, a decoy protein that binds to the NOD SIRPα variant and prevents it from binding to mouse CD47, or isotype control Fc protein (hIgG1 Fc). Recipient mono-DCs in grafts were measured as in Fig. 1. Control untreated recipients (None) from previous experiments are shown for comparison. (B) NOD or BALB/c grafts were transplanted to BRG CD47−/− mice, and the innate alloresponse was compared with that of CD47-sufficient (BRG) recipients from previous experiments. (C and D) Grafts from wild-type (B6 and BALB/c) or mutant (B6 mSIRP-A) mice, which lack the intracellular signaling domain of SIRPα, were transplanted to CRG (C) or BRG (D) recipients to test the effect of removing SIRPα signaling from donor cells on the host response. (E) Proportion of mature (MHCIIhiCD80+) recipient or donor mono-DCs in NRG allografts transplanted to BRG mice. (F) Absolute number of mature host mono-DC in allogeneic (NRG) versus syngeneic (BRG) grafts transplanted to BRG recipients. n = 6 mice per group per experiment. Experiments were performed once or twice. Each dot represents an individual biological replicate. Bars are means. *P < 0.05, **P < 0.01, ****P < 0.0001 (unpaired two-tailed t test). Hehua Dai et al. Sci. Immunol. 2017;2:eaam6202 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.