Fig. 2. Innate immunity, including activation of the ComC and the Nlrp3 inflammasome, orchestrates different steps of hematopoietic transplantation.

Innate immunity mediators, including ComC-derived anaphylatoxins C3a, C5a, and C5b-C9 and the Nlrp3 inflammasome, are important for inducing sterile inflammation in the donor BM during pharmacological mobilization of HSPCs and in the recipient BM after myeloablative conditioning for transplantation by radio/chemotherapy. As depicted here, ComC cleavage fragments and the Nlrp3 inflammasome promote optimal egress of HSPCs from BM into PB (A), promote navigation of HSPCs to BM niches (B), and activate the ComC and expression of Nlrp3 inflammasomes in the BM microenvironment of a transplantation recipient (C), all of which are required for proper homing and engraftment of transplanted cells.