Associate Research Scientist Yale Univ. New Haven, Connecticut, United States
Disclosure(s):
Jing Chen, PhD: No financial relationships to disclose
Introduction/Rationale: Natural killer (NK) cells circulate in the blood in a poised but inactive state and can be further primed by activating signals to acquire enhanced cytotoxicity and secretion of pro-inflammatory cytokines such as IFN-, and TNF-. We hypothesize that NK cells can be primed by migration through endothelial cells (ECs) as they enter graft or tumor tissue.
Methods: Nk cell isolation, Flow cytometry. Trans-endothelial migation assay.
Results: We observed that isolated human blood NK cells will undergo trans-endothelial migration (TEM) through IL-1β-activated but not resting EC monolayers over 60 minutes. Human peripheral blood NK cells showed a rapid rise of P-STAT5 in 20-30 minutes and elevated synthesis of TNF- and Granzyme B after 4-5 days of coculture. IL-15-induced increases of P-STAT5 was inhibited by an anti–IL-15 antibody. Furthermore, we are exploring whether the increased TNF- and IFN- synthesis is inhibited by a pharmacological blocker of HuR binding to their mRNAs.
Conclusion: Elucidating key molecular interactions at the endothelial interface that govern NK cell behavior has potential implications for therapeutic modulation.
