The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.

Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

Background/aim: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies. Materials and methods: We studied KIR and HLA genotypes in 115 related donors and recipients (56 patients with AML and 59 patients with ALL) who had received allo-HSCT from HLA-matched sibling donors. We evaluated 17 KIR genes and some alleles, including their ligands, using the PCR-SSP assay. Results: KIR gene frequency results between donors and recipients showed that donors had more activating KIR than their recipients. Chi-square comparison of KIR genotype frequencies in donors versus recipients revealed a significant difference (P < 0.001). We found a survival association between the donor lacking and the recipient having group B KIR haplotypes, although this was not statistically significant. Conclusion: This study suggests that we could exploit NK cell alloreactivity as a part of the optimization of donor selection and potential immunotherapeutic regimens to help facilitate good engraftment and reduce the risk of aGVHD incidence after allo-HSCT.

Epigenetic involvement in etiopathogenesis and implications in treatment of systemic lupus erythematous.

BACKGROUND: Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors. The recent advances in the field of epigenetics provide a new insight into the understanding of the disease mechanisms, development, diagnostic and prognostic approaches, as well as the various treatment methods. PURPOSE: This review paper aims to present an overview of epigenetic modifications involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss their important roles in clinical and pharmacological settings, including novel and recent therapeutic applications. RESULTS: Nowadays, it is believed that autoimmune diseases, such as SLE, begin when genetically susceptible factors associate with environmental triggers. The current therapeutic approaches for SLE treatment have been based on treatments with immunosuppressive drugs, which are linked to various side effects. It is difficult to develop highly effective treatments for SLE patients with minimal or no side effects, mainly due to the disease complexity. The breakthrough of pharmacoepigenetics provides a new approach to solve this problem. Epigenetic modifications can influence the efficacy of drugs by changing the gene expression through modifying chromatin remodeling. In this regard, epigenetic studies in SLE are expected to reveal novel disease biomarkers and therapeutic targets. CONCLUSIONS: Accumulating evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis and may be exerted as biomarkers to diagnose and as tools to treat these patients.