👤 Catia Traversari

Adolescent idiopathic scoliosis (AIS) is a multifactorial disease with environmental and genetic components. AIS clinical management is complicated by the lack of reliable predictive markers of progression. Recent studies have highlighted a potential role for epigenetic mechanisms in disease progression. However, most findings derive from peripheral blood analyses, with little data available on musculoskeletal tissues directly affected by AIS. Given the tissue-specific nature of epigenetic regulation, validating blood-based biomarkers in disease-relevant tissues is essential. We performed a comparative multi-gene RT-qPCR analysis, arranged in a custom array format, to assess the local expression of candidate epigenetically regulated genes associated with AIS progression across bone, paravertebral muscle, spinal ligament, and peripheral blood, all collected from the same patients. Tissue- and gene-specific expression patterns were observed, supporting the presence of local regulatory mechanisms. Peripheral blood expression of Show less

Oxysterols are involved in maintaining cellular cholesterol levels. Recently, oxysterols have been demonstrated to modulate the function of immune cells and tumor growth. These effects can be dependent on the activation of the oxysterol-binding liver X receptors (LXRs) or, as recently demonstrated for T and B cells, DCs and neutrophils, can be independent of LXR activation. LXR-dependent oxysterol effects can be ascribed to the activation of LXRα, LXRβ or LXRαβ isoforms, which induces transcriptional activation or trans-repression of target genes. The prevalent activation of one isoform seems to be cell-, tissue-, or context-specific, as shown in some pathologic processes, i.e., infectious diseases, atherosclerosis, and autoimmunity. Oxysterol-LXR signaling has recently been shown to inhibit antitumor immune responses, as well as to modulate tumor cell growth. Here, we review the mechanisms that link oxysterols to tumor growth, and discuss possible networks at the basis of LXR-dependent and -independent oxysterol effects on immune cells and tumor development. Show less

Oxysterols/oxysterol receptors have been shown to modulate several immune cell subsets, such as macrophages, T-cells and B-cells, neutrophils and dendritic cells (DCs). They participate in the control of several pathologic processes, that is, infectious diseases, atherosclerosis and autoimmunity. Moreover, some oxysterols have also been shown to favor tumor progression by dampening the antitumor immune response. The cellular responses generated by oxysterols depend on the engagement of Liver X Receptor (LXR) α and/or β isoforms, which induce activation of target genes or trans-repression of pro-inflammatory gene transcription. Recently, some reports have described a different mechanism of action of oxysterols, mediated by the engagement of G-Protein Coupled Receptors. Here, we summarize LXR-dependent and LXR-independent responses of oxysterols on immune cells with possible effects on tumor development. Show less

Sterol metabolism has recently been linked to innate and adaptive immune responses through liver X receptor (LXR) signaling. Whether products of sterol metabolism interfere with antitumor responses is currently unknown. Dendritic cells (DCs) initiate immune responses, including antitumor activity after their CC chemokine receptor-7 (CCR7)-dependent migration to lymphoid organs. Here we report that human and mouse tumors produce LXR ligands that inhibit CCR7 expression on maturing DCs and, therefore, their migration to lymphoid organs. In agreement with this observation, we detected CD83(+)CCR7(-) DCs within human tumors. Mice injected with tumors expressing the LXR ligand-inactivating enzyme sulfotransferase 2B1b (SULT2B1b) successfully controlled tumor growth by regaining DC migration to tumor-draining lymph nodes and by developing overt inflammation within tumors. The control of tumor growth was also observed in chimeric mice transplanted with bone marrow from mice lacking the gene encoding LXR-alpha (Nr1h3(-/-) mice) Thus, we show a new mechanism of tumor immunoescape involving products of cholesterol metabolism. The manipulation of this pathway could restore antitumor immunity in individuals with cancer. Show less