1,721,000 research outputs found
Signaling Crosstalks Drive Generation and Regeneration of the Thymus
No full textOptimal recovery of immune competence after periods of hematopoietic insults or stress is crucial to re-establish patient response to vaccines, pathogens and tumor antigens. This is particularly relevant for patients receiving high doses of chemotherapy or radiotherapy, who experience prolonged periods of lymphopenia, which can be associated with an increased risk of infections, malignant relapse, and adverse clinical outcome. While the thymus represents the primary organ responsible for the generation of a diverse pool of T cells, its function is profoundly impaired by a range of acute insults (including those caused by cytoreductive chemo/radiation therapy, infections and graft-versus-host disease) and by the chronic physiological deterioration associated with aging. Impaired thymic function increases the risk of infections and tumor antigen escape due to a restriction in T-cell receptor diversity and suboptimal immune response. Therapeutic approaches that can promote the renewal of the thymus have the potential to restore immune competence in patients. Previous work has documented the importance of the crosstalk between thymocytes and thymic epithelial cells in establishing correct architecture and function of thymic epithelium. This crosstalk is relevant not only during thymus organogenesis, but also to promote the recovery of its function after injuries. In this review, we will analyze the signals involved in the crosstalk between TECs and hematopoietic cells. We will focus in particular on how signals from T-cells can regulate TEC function and discuss the relevance of these pathways in restoring thymic function and T-cell immunity in experimental models, as well as in the clinical setting
Genomic and non genomic effects of different glucocorticoids in mouse thymocytes apoptosis
No full textClinical strategies to enhance thymic recovery after allogeneic hematopoietic stem cell transplantation
No full textThe thymus is particularly sensitive to injury caused by cytoreductive chemo- or radiation therapy, shock, infection and graft versus host disease. Insufficient thymic recovery has been directly correlated with increased risk of opportunistic infections and poor clinical outcomes in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Prolonged immune deficiency is particularly pronounced in older patients whose thymi are already significantly impaired due to age-related thymic involution. Preclinical and clinical studies have revealed several strategies that can enhance thymic function and immune reconstitution after transplant, including sex steroid ablation, growth factors (growth hormone, keratinocyte growth factor, insulin-like growth factor 1, interleukin-7) and ex vivo generated precursor T cells. In addition, recent studies have shown that other approaches, such as interleukein-22 and nutritional changes, may represent additional candidates to enhance thymic regeneration. In this review we provide updates on these strategies and comment on their potential to be translated into clinical therapies
The Glucocorticoid-Induced Leucin Zipper (GILZ) protects against DNBS-induced colitis development
No full textRole of Glucocorticoid-Induced Leucine Zipper (GILZ) in the controls of inflammation induced by spinal cord injury
No full textGlucocorticoid-Induced Leucine Zipper (GILZ) and Long GILZ Inhibit Myogenic Differentiation and Mediate Anti-myogenic Effects of Glucocorticoids
No full textMyogenesis is a process whereby myoblasts differentiate and fuse into multinucleated myotubes, the precursors of myofibers. Various signals and factors modulate this process, and glucocorticoids(GCs)areimportantregulators of skeletal muscle metabolism. We show that Glucocorticoid-Induced Leucine Zipper (GILZ), a GC-induced gene, and the newly identified isoform Long-GILZ (L-GILZ) are expressed in skeletal muscle tissue and in C2C12 myoblasts where GILZ/L-GILZ maximum expression occurs during the first few days in differentiation medium. Moreover, we observed that GC treatment of myoblasts, which increased GILZ/L-GILZ expression, resulted in reduced myotubes formation while GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ over-expression correlated with inhibition of MyoD function and reduced expression of myogenin. Notably, results indicate that GILZ and L-GILZ bind and regulate MyoD/HDAC1 transcriptional activity thus mediating the anti-myogenic effect of GCs
The Glucocorticoid-Induced Leucin Zipper (GILZ) protects against DNBS-induced colitis development
No full textThe Glucocorticoid-Induced Leucine Zipper (GILZ) inhibits skeletal myogenesis by counteracting MyoD activity
No full textRole of Glucocorticoid-Induced Leucine Zipper (GILZ) in the controls of inflammation induced by spinal cord injury
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