A study published in The New England Journal of Medicine confirms that interleukin 10 is the most important immunomodulatory cytokines in the intestine. Furthermore, it has been shown that mutations in the gene that encodes some of its proteins in patients with early stages of inflammatory bowel disease.
Patients in the early stages of enter colitis have mutations in the genes encoding protein subunits of IL-10R, which implies an immune response in the intestine hyper inflammatory. The stem cell transplant achieved a remission in a patient, according to results of a study to advance the New England Journal of Medicine.
The group of Christoph Klein, Department of Pediatric Hematology and Oncology College of Medicine in London, has conducted an analysis of genetic relationship and sequencing of candidate genes of two unrelated consanguineous families. Furthermore, this equipment is studied in six additional patients with the early stages of inflammatory bowel disease mutations in two genes candidates who conducted functional analysis of peripheral blood cells mononuclear.
In four of the nine patients in the early stages of colitis were identified homozygous mutations in the genes IL-10RA and IL-10RB, which encode proteins IL-10R1 and IL-10R2, forming a heterotetramer comprising receptors IL-10. Mutations eliminating the signaling pathways of IL-10 and cause a deficiency of Stat3 phosphorylation on stimulation with IL-10.
Activation
As a result of this process, increased secretion of tumor necrosis factor alpha and other proinflammatory cytokines from peripheral blood mononuclear cells in patients deficient in protein subunits of IL-10R, suggesting that dependent regulation of IL-10 is impaired in these cells.
In an editorial also published in The New England Journal of Medicine, Brian Kelsall, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, U.S., says the study is related to the results of work in mouse model indicating that IL-10 is the most important immunomodulatory cytokines in the intestine and acts in principle in hematopoietic cells.
The work suggests a new research source for IL-10, their receptors and signaling pathways in understanding the pathogenesis of inflammatory bowel disease and also serves to re-evaluate therapeutic strategies.
Tags: hyper inflammatory, IL-10R, inflammatory bowel disease, Medicine, Molecular Immunology
