Immunomodulation by adipokines in type 1 diabetes

Chimen, Myriam (2012). Immunomodulation by adipokines in type 1 diabetes. University of Birmingham. Ph.D.

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Abstract

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:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):