melihtas
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http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3842.html
Full Text is behind paywall.
Article about the paper:
http://www.birmingham.ac.uk/news/latest/2015/04/Newly-discovered-pathway-200415.aspx
Full Text is behind paywall.
Homeostatic regulation of T cell trafficking by a B cell–derived peptide is impaired in autoimmune and chronic inflammatory disease
Abstract
During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.
Article about the paper:
http://www.birmingham.ac.uk/news/latest/2015/04/Newly-discovered-pathway-200415.aspx
Newly discovered pathway reveals how our immune system is regulated; gives hope for serious chronic diseases
Researchers from the University of Birmingham have identified an important new way in which our immune systems are regulated, and hope that understanding it will help tackle the debilitating effects of type 1 diabetes, rheumatoid arthritis and other serious diseases.
The team discovered a novel pathway that regulates the movement of pathogenic immune cells from the blood into tissue during an inflammatory response.
A healthy, efficient immune system ordinarily works to damp down inflammation and carefully regulate the magnitude of the response to infection and disease. In diseases such as diabetes and arthritis, as well as when we age, our immune system becomes less stringently regulated and this can lead to an exaggerated inflammatory response – allowing inappropriate access of immune cells to vulnerable tissues. The new study shows that beneficial effects of the new pathway are lost in these diseases, as well as during normal ageing.
The study, published in Nature Medicine, details how a key molecule regulates this aspect of our immune response. Importantly, the team were then able to show how the addition of this molecule to immune cells from patients with diabetes and arthritis could regain control of the movement of their immune cells, thereby reversing the pathogenic changes seen in these diseases.