Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation.
Cells CD4 + T helper cells able to differentiate into several subsets effector perform diverse functions during the adaptive immune response. Each subset differentiation is regulated, largely, by environmental cytokine signaling and subsequent activation of downstream transcription factor network of cell-intrinsic.
Ikaros zinc finger (IkZF) transcription factor known regulator of the development of immune cells, including CD4 + T cell subset Over the past decade, members of the family IkZF also been involved in the differentiation and function of T helper cell subset of individuals, including the T helper 1 (THHHFH ) and regulatory (Treg) cells T. Now, an increasing body of literature suggests that cell-specific cytokine different environment which is responsible for the development of any part results in differential expression IkZF factor of the entire population of T helper.
Interestingly, recent studies have shown that members of IkZF affects T helper differentiation inside the feed-forward mode through the regulatory cytokine-signaling pathways are the same. Here, we review the increasingly important role for IkZF transcription factor in the differentiation of effector CD4 + T helper cell subsets.
Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation.
Assessing Relevance of Functional Variants in IKAROS Family Zinc Finger Protein 1 (IKZF1) in Cohort Patients With Primary Immunodeficiency.
common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency. Patients with CVID are susceptible to recurrent bacterial infections because of a failure of adequate immunoglobulin production. monogenetic defects have been identified in ~ 25% of patients with CVID.
More recently, mutations in IKZF1, encoding zinc-finger transcription factor IKAROS widely expressed in hematopoietic cells, has been associated with CVID like phenotype. Here we describe 11 patients with heterozygous variant IKZF1 of eight different families with autosomal dominant CVID and two siblings with a variant IKZF1 with inflammatory bowel disease (IBD). This study shows that the mutation affects the DNA binding domain IKAROS can disrupt the interaction with the target DNA sequence so as to prevent and localization pericentromeric heterochromatin (HC-PC) protein. Our results also indicate a decrease in localization pericentromeric of IKAROS by overexpression of truncated variants, due to mature stop codon in IKZF1.
We also describe additional variant in TNFSF10, encoding Tumor Necrosis Factor Related Apoptosis Encouraging ligand (TRAIL), also served in the individuals of A. Our Families results show that these variants can disrupt TRAIL-induced apoptosis in the target cell line and forbid the activation of NF by TRAIL and can act as a modifier in Family A We report a new variant in IKZF1 associated with IKAROS haploinsufficiency in patients with familial immune thrombocytopenia (ITP). IKAROS, encoded by the gene IKZF1, a zinc-finger transcription factor hematopoietic can directly bind to DNA.
Description: Gastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic factor for gastrointestinal epithelial cells. Gastrin has two biologically active peptide forms, G34 and G17.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
Description: Gastrin, is a hormone that normally formed by mucosal cells in the gastric antrum and by the D cells of the pancreatic islets. Its primary function is to stimulate secretion of HCl by the gastric mucosa. HCl, in turn, inhibits gastrin formation. It also responsible for stimulating smooth muscle contraction and increasing blood circulation and water secretion in the stomach and intestine. Gastrin is regulated by epidermal growth factor in both mice and humans. Gastrin is excreted in excess by pancreatic tumors in the Zollinger-Ellison syndrome. Gastrin-Releasing Peptide (GRP) stimulates the release of gastrin as well as other gastrointestinal hormones and also acts as an autocrine growth factor for certain cell types. High levels of GRP are found in the human lung just after birth and levels decrease thereafter in parallel with the observed disease in a number of pulmonary neuroendocrine cells. GRP is known to promote lung tumorigenesis in model systems.
We show that the variants identified IKZF1 (p.His195Arg) alter histidine residues absolutely conserved required for folding of the three zinc-finger protein IKAROS, lead to the loss of the characteristics of nuclear immunofluorescence staining pattern. In our case, genetic testing is essential for diagnosis IKAROS haploinsufficiency, the presentation of which are known, including infections, aberrant hematopoiesis, leukemia, and age-related decline in humoral immunity. Our family studies underscore that, after infection, ITP is the most common clinical manifestation of both IKAROS haploinsufficiency.
