Project description:We analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells. We identified a set of 1414 Affymetrix probe sets showing significant misregulation (Welch's T-test, p<0.05; Benjamini-Hochberg FDR corrected). IL-18 generated as well as unstimulated NK cells were isolated in three independent preparations and used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:We analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells. We identified a set of 1414 Affymetrix probe sets showing significant misregulation (Welch's T-test, p<0.05; Benjamini-Hochberg FDR corrected).
Project description:NK cells are an emerging cancer cellular therapy and potent mediators of anti-tumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in acute myeloid leukemia (AML) patients. However, the dynamic molecular changes that occur after memory-like differentiation in vitro are unclear. Here, control or ML NK cells purified from normal donor PBMC were generated in vitro. Briefly, RosetteSep-purified NK cells were incubated in IL-12, IL-15, and IL-18, or low-dose IL-15 as a control for 16-18 hours. Control or cytokine-activated NK cells were washed three times and cultured for 6 days in low-dose IL-15, which is required for NK cell survival. After 6 days, RNA was isolated from control and memory-like (ML) NK cells (IL12/15/18 activation) and RNA-sequencing performed. Because the transcription factor GATA-3 was increased specifically in ML NK cells, we hypothesized ML NK cells would exhibit a GATA-3 gene signature compared to control NK cells. Indeed, using GSEA, a significant gene signature was associated with ML NK cell differentiation. These data support the role for GATA-3 in regulating the ML NK cell molecular program.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Cancer-induced tolerance mostly involves myeloid suppressor cells, regulatory T cells and immunosuppressive cytokines, which all subvert adaptive immune responses against tumor cells. Here, we show that a subset of innate effectors, c-kit expressing NK cells (Kit+ NK), can participate in tumor-induced tolerance by compromising the NK cell arm of tumor immunosurveillance. IL-18 produced by tumor cells can convert Kit- into Kit+ NK cells that overexpress B7-H1/PD-L1 molecules. Upon tumor inoculation, Kit+ NK cells rapidly develop in lymphoid organs in a IL-18R/MyD88 dependent manner and directly kill Kit- NK cells in a B7-H1/PD-1-dependent manner, thereby promoting the progression of NK-controlled cancers. Our data suggest that, in a tumoral context, IL-18 subverts antitumor NK cell functions. Systemic neutralization of IL-18 by IL-18-binding protein may improve the NK-mediated immunosurveillance. Keywords: cell type comparison