Session 3, Abstract 14
DETERMINING THE ROLE OF SOSTDC1 IN NATURAL KILLER CELL FUNCTION.
Sonny Elizaldi*, Albert Jovani Millan, Eric Lee and Gabriela Loots (Jennifer O. Manilay), University of California Merced, 5200 N. Lake Rd., Merced, CA 95340.
Natural Killer (NK) cells are innate-like lymphocytes that eliminate cancerous and virally infected cells. A developmentally linear sequence for NK cell maturation has recently emerged: immature NK (iNK:CD27+CD11b), transitional NK (tNK: CD27+CD11b+), and most mature (mNK:CD27- CD11b+). NK cells randomly express Ly49 activating and inhibitory surface receptors through mechanisms that are not fully understood. Currently Ly49 receptor expression is known to be partially controlled by major histocompatibility complex class I (MHC-I) and cytokines. Sclerostin domain-containing-1 protein (Sostdc1) is a Wnt and Bmp signaling antagonist, but its function in immune cell development has not been investigated. Using a Sostdc1-LacZ reporter knock-in mouse model and reciprocal bone marrow transplantation assays, our laboratory has discovered that complete deletion of Sostdc1 alters NK cell development and Ly49 expression in a cell intrinsic manner. Using RT-PCR, we have confirmed Sostdc1 expression in WT iNK cells and expression of LacZ in KO iNK cells, further suggesting a cell-intrinsic effect of Sostdc1 in NK cells. We hypothesize that loss of Sostdc1 will adversely affect NK cell activation and degranulation. To test this hypothesis, we conducted an in-vitro NK cell stimulation assay using PMA and ionomycin, and measured expression of CD107a (LAMP1) and production of IFNg using flow cytometry. Our data demonstrates that after stimulation, both Sostdc1KO and WT NK cells are skewed towards the mNK cell state. However, the higher frequencies of WT mNK cells in comparison to the KO suggests that the lack of Sostdc1 results in a developmental blockade from tNK to mNK cell populations.