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Tolerogenic Dendritic Cell
Tolerogenic dendritic cells (a. k. a. tol-DCs, tDCs, or DCregs) are heterogenous pool of dendritic cells with immuno-suppressive properties, priming immune system into tolerogenic state against various antigens. These tolerogenic effects are mostly mediated through regulation of T cells such as inducing T cell anergy, T cell apoptosis and induction of Tregs. Tol-DCs also affect local micro-environment toward tolerogenic state by producing anti-inflammatory cytokines. Tol-DCs are not lineage specific and their immune-suppressive functions is due to their state of activation and/or differentiation. Generally, properties of all types of dendritic cells can be highly affected by local micro-environment such as presence of pro or anti-inflammatory cytokines, therefore tolerogenic properties of tol-DCs are often context dependant and can be even eventually overridden into pro-inflammatory phenotype. Tolerogenic DCs present a potential strategy for treatment of autoimmune diseases, aller ...
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Dendritic Cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the ''dendrites'' that give the cell its name (δένδρον or déndron being Greek for 'tree'). While similar in appearance, these are structures disti ...
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Heme Oxygenase 1
''HMOX1'' (heme oxygenase 1 gene) is a human gene that encodes for the enzyme heme oxygenase 1 (). Heme oxygenase (abbreviated HMOX or HO) mediates the first step of heme catabolism, it cleaves heme to form biliverdin. The ''HMOX'' gene is located on the long (q) arm of chromosome 22 at position 12.3, from base pair 34,101,636 to base pair 34,114,748. Related conditions * Heme oxygenase-1 deficiency Heme oxygenase Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, carbon monoxide, and ferrous iron. The biliverdin is subsequently converted to bilirubin by biliverdin reductase. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. See also * HMOX2 * Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis (FSGS) is a histopatholog ...
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Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. Some common naturally occurring steroid hormones are cortisol (), corticosterone (), cortisone () and aldosterone (). (Note that cortisone and aldosterone are isomers.) The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. Classes * Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive effects. Anti-inflammatory effects are mediated by blocking the action of inflammatory medi ...
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Vitamin D3
Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D that is made by the skin when exposed to sunlight; it is found in some foods and can be taken as a dietary supplement. Cholecalciferol is made in the skin following UVB light exposure. It is converted in the liver to calcifediol (25-hydroxyvitamin D) which is then converted in the kidney to calcitriol (1,25-dihydroxyvitamin D). One of its actions is to increase calcium uptake by the intestines. It is found in food such as some fish, beef liver, eggs, and cheese. Plant and cow milk, fruit juice, yogurt, and margarine also may have cholecalciferol added to them in some countries, including the United States. Cholecalciferol can be taken as an oral dietary supplement to prevent vitamin D deficiency or as a medication to treat associated diseases, including rickets. It is also used for familial hypophosphatemia, hypoparathyroidism that is causing low blood calcium, and Fanconi syndrome. Vitam ...
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Retinoic Acid
Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-''trans''-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. All-''trans''-retinoic acid (ATRA) is the major occurring retinoic acid, while isomers like 13-''cis''- and 9-''cis''-retinoic acid are also present in much lower levels. The key role of all-''trans''-retinoic acid in embryonic development mediates the high teratogenici ...
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Vasoactive Intestinal Peptide
Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the ligand of class II G protein–coupled receptors. VIP is produced in many tissues of vertebrates including the gut, pancreas, and suprachiasmatic nuclei of the hypothalamus in the brain. VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gallbladder. In humans, the vasoactive intestinal peptide is encoded by the ''VIP'' gene. VIP has a half-life (t½) in the blood of about two minutes. Function In the body VIP has an effect on several tissues: In the digestive system, VIP seems to induce smooth muscle relaxation (lower esophageal sphincter, stomach, gallbladder), stimulate secretion of water into pancreatic juice a ...
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Hepatocyte Growth Factor
Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells and T cells. It has been shown to have a major role in embryonic organ development, specifically in myogenesis, in adult organ regeneration, and in wound healing. Function Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration. Structure It is secreted as a single inactive polypeptide and is ...
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Interleukin 27
Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric cytokine that is encoded by two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by antigen presenting cells and interacts with a specific cell-surface receptor complex known as IL-27 receptor (IL-27R). This receptor consists of two proteins, IL-27ɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10. Signal transduction When IL-27 binds to the IL-27 receptor, signaling pathways including JAK-STAT and p38 MAPK pathways are turned on. There are two types of responses, pro-inflammatory and anti-inflammatory, which involve different types of cells, such as macrophages, dendritic cells, T cells, and B cells. The response that is activated is very much dependent on the external surrounding of IL-27. Differentiation of T cells There are many different subsets of T cells, such a ...
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Indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO ) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the ''IDO1'' gene. IDO is involved in tryptophan metabolism. It is one of three enzymes that catalyze the first and rate-limiting step in the kynurenine pathway, the O2-dependent oxidation of L-tryptophan to N-formylkynurenine, the others being indolamine-2,3-dioxygenase 2 (IDO2) and tryptophan 2,3-dioxygenase (TDO). IDO is an important part of the immune system and plays a part in natural defense against various pathogens. It is produced by the cells in response to inflammation and has an immunosuppressive function because of its ability to limit T-cell function and engage mechanisms of immune tolerance. Emerging evidence suggests that IDO becomes activated during tumor development, helping malignant cells escape eradication by the immune system. ...
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IL-10 Family
The IL10 family is a family of interleukins. In addition to IL-10, it includes IL-19, IL-20, IL-22, IL-24 and IL-26. Some sources also include the interferons IL-28 and IL-29. The IL-10 family are helical cytokines categorized based on their specific similarities and can be classified as class 2 cytokines. IL-10 Family Biological activity IL-10 family - is one of the important types of cytokines, that can stop the inflammation. In general. these cytokines have a helical structure of homodimers. The difference that the members of IL-10 family have between each other is that they have various receptor-binding residues, which help with interaction with specific cytokine receptors. The features of the IL-10 family consists of their genomic structure being similar, their primary and secondary protein structures being similar, their a clustering of encoding genes, and their utilization the similar receptor complexes. IL-10 Interleukin 10 is produced by regulatory T ly ...
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DC-SIGN
DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 ( Cluster of Differentiation 209) is a protein which in humans is encoded by the ''CD209'' gene. DC-SIGN is a C-type lectin receptor present on the surface of both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds with high affinity to high-mannose type N-glycans, a class of PAMPs (pathogen associated molecular patterns) commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis. On myeloid and pre-plasmacytoid dendritic cells DC-SIGN mediates dendritic cell rolling interactions with blood endothelium and activation of CD4+ T cells, as well as recognition of pathogen haptens. Function DC-SIGN is a C-type lectin and has a high affinity for the ICAM3 molecule. It binds various microorganisms by recognizing high-mannose-containing glycoproteins on their surface, and can function as a co-receptor for several ...
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Galectin-1
Galectin-1 is a protein that in humans is encoded by the ''LGALS1'' gene. Gene and protein LGALS1 contains four exons. The galectin-1 protein is 135 amino acids in length and highly conserved across species. It can be found in the nucleus, the cytoplasm, the cell surface and in the extracellular space. Galectins in general lack a traditional signal sequence, but are still secreted across the plasma membrane. This non-traditional secretion requires a functional glycan binding site. Galectin 1 contains a single carbohydrate recognition domain through which it can bind glycans both as a monomer and as a homodimer. Dimers are non-covalently bound and will spontaneously disassociate in low concentration. Galectin 1 does not bind glycans when oxidized. Having 6 cysteine residues, the oxidation state has a significant effect on the protein structure. The oxidized form is reported to have alternative functions not involving carbohydrate binding. Function The galectins are a family ...
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