Project description:RNA-seq technology was confirmed that mRNA and LncRNA expression have an important role in vaccine adjuvant in vivo and in vitro. Kynurenin, as an immunosuppressive adjuvant, but the exact mechanism of action with immune cells is still poorly understood. In the present study, mRNA and lncRNA sequencing was performed in mouse splenocytes stimulated by Kynurenin. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant regulated the immune response.
Project description:RNA-seq technology was confirmed that miRNA expression has an important role in vaccine adjuvant in vivo and in vitro. Kynurenin, as an immunosuppressive adjuvant, but the exact mechanism of action with immune cells is still poorly understood. In the present study, RNA and miRNA sequencing was performed in mouse splenocytes stimulated by Kynurenin. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant regulated the immune response.
Project description:We report the gene expression (obtained by next generation RNAseq) of inducible CD103+ dendritic cells, iCD103 cells, stimulated with both murine herpesvirus-68 and the immunomodulatory tryptophan derivative kynurenine (kyn). This study provides data on how tryptophan derivatives can modulate pro-inflammatory cytokine expression in virus treated dendritic cells.
Project description:Kynurenine is generated from tryptophan by indoleamine 2,3-dioxygenase (IDO1) and binds to the aryl hydrocarbon receptor (AhR). We found that kynurenine generated by human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) stimulated the AhR to bind selectively to the promoters and enhancers of self-renewal genes, thus enhancing their transcription. The kynurenine-AhR complex also directly stimulated the expression of IDO1 and AHR, activating a positive feedback loop. Substantial amounts of kynurenine that were not complexed with AhR were present in the culture medium, providing a paracrine signal for maintenance of the undifferentiated state. Kynurenine was not present in the medium of differentiated ESCs and iPSCs. When cells were induced to undergo ectodermal differentiation, the abundance of kynurenine in the medium was reduced through activation of the main kynurenine catabolic pathway mediated by aminotransferase 2 (KAT2), resulting in the secretion of 2-aminoadipic acid (2-AAA) into the culture medium. Thus, kynurenine in the culture medium is a biomarker for the undifferentiated state, and 2-AAA in the culture medium is a biomarker for ESCs and iPSCs that have committed to differentiate along the ectoderm lineage.
Project description:Immortalized mouse macrophages (IMMs) were stimulated with lipopolysaccharide (LPS). RNA and RNA associated proteins were UV crosslinked, and sites of RNA-association were identified using LC-MS proteomics.
Project description:Uterine leiomyoma (LM) is the most common tumor in women. Estrogen and progesterone, via their receptors ERα and PR, play essential roles in LM growth. Mediator complex subunit 12 (MED12) mutations occur in 70% of all LM and are thought to drive tumor growth in a steroid hormone-dependent manner; however, the mechanisms remain unclear. Here, we performed ChIP-seq (ERα, PR, and MED12) and RNA-seq on LM expressing mutant MED12 (mut-MED12) or wild-type MED12 and matched myometrium. Mut-MED12 altered PR and chromatin interaction landscapes, with significant PR-binding site loss in proximal promoter regions in mut-MED12 LM. Integration of cistrome and transcriptome data identified tryptophan 2,3-dioxygenase (TDO2) as a PR and MED12 target gene, which was aberrantly upregulated in mut-MED12 LM. Kynurenine, the catabolic product of TDO2, was significantly elevated in mut-MED12 LM. Tryptophan or kynurenine treatment of primary LM cells activated the aryl hydrocarbon receptor (AHR) pathway, increased cell proliferation, and inhibited apoptosis; blocking the TDO2-kynurenine-AHR pathway by siRNA knockdown or pharmacologic inhibition abolished these effects. Mut-MED12 LM cells showed higher sensitivity to these treatments. These findings suggest that activation of the TDO2-kynurenine-AHR pathway in mut-MED12 LM induces tumor growth, and may inform the development of targeted treatments and precision medicine in LM.