Part of the book: Advances in Hematopoietic Stem Cell Research
Part of the book: Stem Cell Biology in Normal Life and Diseases
Part of the book: Trends in Basic and Therapeutic Options in HIV Infection
Treg cells CD4+CD25+FOXP3+ have a specific function in the tolerance of autoantigens and regulation of the immune response. Modulation of differentiation pathways and the use of Treg cells in cell therapy have been reported in autoimmune diseases, systemic lupus erythromatosis, autoimmune hepatitis, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, bone marrow transplantation and solid organs. The expansion of Treg cells in vivo occurs through low-dose IL-2 treatment. However, because of the heterogeneity and variability of Treg cells, the isolation of peripheral blood cells, through the technique of leucopheresis by GMP (good manuring practice), for in vitro expansion is difficult, necessitating a large combination of specific and reliable cellular markers. Currently, two specific markers, Helios and neuropilin-1, are being studied to facilitate the differentiation of thymus Treg cells and peripheral Treg cells. However, Treg cells induced in vitro are unstable. Modulation of the FOXP3 gene in the CNS1 and CNS2 region is an alternative to maintaining the stability of expanded Treg cells in vitro.
Part of the book: Lymphocyte Updates
The metabolism of iron is regulated by the peptide hormone hepcidin. Genetic alterations in the proteins involved in the signalling pathway and hepcidin transcription cause damage to the organism. Mutations and polymorphisms in the hepcidin antimicrobial peptide(HAMP), HFE, HJV, ferroportin and matriptase-2 genes influence serum hepcidin concentration. Genetic deficiency of hepcidin increases iron overload in tissues, leading to haemochromatosis. However, genetics changes in the TMPRSS6 gene promote an increase in serum hepcidin, with the development of severe anaemia and resistance to iron treatment, as observed in IRIDA. Making the flow and efflux of extracellular and intracellular iron is impossible. To date, no drug that works by inhibiting or enhancing hepcidin transcription is available, largely because of the cytotoxicity described in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials, some are good candidates, such as heparin derivatives and mini-hepcidins.
Part of the book: Genetic Polymorphisms
Anemia presents a global public health problem. It is related to several factors, ranging from deficiency in nutrients from food to genetic alterations in iron absorption and metabolism. In this context, hepcidin is a peptide molecule that regulates iron homeostasis. Hepcidin is synthesized, in part, by hepatocytes. In physiological conditions, increased serum transferrin, serum iron, inflammation, and erythropoiesis trigger stimuli that promote hepcidin antimicrobial peptide (HAMP) gene transcription and hepcidin synthesis. However, in pathological situations, an overexpression of hepcidin occurs, an increase in the plasma concentration that damages the organism. Hepcidin contributes to the pathogenesis of iron deficiency anemia, anemia of inflammation, in hemoglobinopathies. Then, there is a restriction of the availability of iron to the tissues and the formation of new erythroid precursors, with the consequent development of anemia.
Part of the book: Current Topics in Anemia