Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts

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Science Immunology  23 Jun 2017:
Vol. 2, Issue 12, eaam6202
DOI: 10.1126/sciimmunol.aam6202

Looking beyond MHCs in transplant rejection

Mice engineered to lack T, B, and NK cells generate mature dendritic cells in response to allogeneic transplants. Precisely how these mice recognize allografts to be “nonself” has remained a mystery. Using an elegant positional cloning approach, Dai et al. have identified polymorphisms in the mouse gene encoding signal regulatory protein α (SIRPα) to be key in this innate self-nonself recognition. They show that SIRPα receptor CD47 binds SIRPα variants with distinct affinities and propose this affinity sensing to be the mechanism that triggers dendritic cell maturation, the first step in the initiation of the alloimmune response. Given that the SIRPα gene is also polymorphic in humans, it remains to be seen whether human SIRPα variations influence transplantation success.

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