Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity.

Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naive immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific and sex-specific. Bioinformatic analysis of the genetically controlled transcript networks reveals reduced cell type specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS (genome-wide association study candidate genes for MS susceptibility) genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared with PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T-cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease. Genes Immun 2016 Dec; 17(7):386-395

Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation

Tumorimmunolog

Cell death in cancer in the era of precision medicine

Tumors constitute a large class of diseases that affect different organs and cell lineages. The molecular characterization of cancers of a given type has revealed an extraordinary heterogeneity in terms of genetic alterations and DNA mutations; heterogeneity that is further highlighted by single-cell DNA sequencing of individual patients. To address these issues, drugs that specifically target genes or altered pathways in cancer cells are continuously developed. Indeed, the genetic fingerprint of individual tumors can direct the modern therapeutic approaches to selectively hit the tumor cells while sparing the healthy ones. In this context, the concept of precision medicine finds a vast field of application. In this review, we will briefly list some classes of target drugs (Bcl-2 family modulators, Tyrosine Kinase modulators, PARP inhibitors, and growth factors inhibitors) and discuss the application of immunotherapy in tumors (T cell-mediated immunotherapy and CAR-T cells) that in recent years has drastically changed the prognostic outlook of aggressive cancers. We will also consider how apoptosis could represent a primary end point in modern cancer therapy and how “classic” chemotherapeutic drugs that induce apoptosis are still utilized in therapeutic schedules that involve the use of target drugs or immunotherapy to optimize the antitumor response