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Immunomodulation by adipokines in type 1 diabetes

Chimen, Myriam (2012)
Ph.D. thesis, University of Birmingham.

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Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the immune system specifically targets and destroys the pancreatic insulin-producing beta-cells. We are interested in defining whether adipose tissue-derived cytokines (adipokines) such as adiponectin (anti-inflammatory) and leptin (pro-inflammatory) could influence T1D progression.

We demonstrate the expression of the leptin receptor (LEPR) on peripheral blood mononuclear cells (PBMC) and observed higher expression of LEPR on PBMC from patients with T1D. However, we found no significant functional relevance for this observation. On the other hand, we show lower expression of the adiponectin receptors on lymphocytes from patients with T1D. This was associated with a reduced capacity of adiponectin to inhibit lymphocyte trans-endothelial migration in T1D. We show that adiponectin strongly inhibited lymphocyte migration by action on the endothelium or directly on the lymphocytes. We have now established that adiponectin action is not directly targetting the lumphocytes but involves accessory cells that express higher level of the adiponectin receptors. These findings were validated \(in\) \(vivo\) using a peritonal model of inflammation and led to the discovery a newly idnetified agent able to control the transmigration of T cells.

These observations underline the importance of adiponectin in the control of lymphocyte transmigration during an inflammatory response and offer a potential therapeutic agent for T cell mediated diseases.

Type of Work:Ph.D. thesis.
Supervisor(s):Narendran, Parth and Lane, Peter
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:QR180 Immunology
Institution:University of Birmingham
ID Code:3581
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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