HSCs are activated by pattern recognition receptors (PRRs), which might provide novel targets for improved engraftment. How PRRs affect HSC engraftment after BM transplantation is not yet known. Our study assessed whether the ASC and Nlrp3 inflammasome adaptor components are expressed in HSCs and whether their absence impacts allogeneic HSC engraftment.

Methods: ASC and Nlrp3 expression in isolated HSCs was determined using qPCR. BALB/c recipient mice were preconditioned with sub-lethal TBI, anti-CD8 and anti-CD40L, followed by allogeneic BM transplant from C57BL/6, ASC-/-, or Nlrp3-/- donors (n=6/gp). Engraftment of HSCs was assessed by FACs analysis of recipient peripheral blood cells (PBCs).

Results: HSCs from C57BL/6 WT donor mice expressed both ASC and Nlrp3 inflammasome components, although relatively more ASC was present in the HSCs. Interestingly, HSCs lacking the ASC inflammasome component engrafted significantly more efficiently into allogeneic hosts than those lacking Nlrp3.

Conclusion: We found differential constitutive expression of the inflammasome components in HSCs from WT mice. Between both adaptor components, HSCs from mice lacking ASC, but not Nlrp3, exhibit a significantly increased ability to engraft into an allogeneic host following BM transplantation. Greater relative expression of ASC versus Nlrp3 in HSCs and significant increase in the ability of ASC-/- HSCs to engraft in allogeneic hosts suggests that ASC might provide a novel target to improve the engraftment of HSCs in allogeneic hosts.

Figure 1:Lower expression of ASC and Nlrp3 in HSCs relative to lymphocytes (n=24/gp). HSCs and lymphocytes isolated from WT C57BL/6 BM and lymph nodes, respectively. Protein expression levels were analyzed using quantitative RT-PCR

« Back to 2015 American Transplant Congress