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Inflammation and Immunology

The following people are in this group:

More about this group

The Inflammation and Immunology group is led by Dr Jim Middleton.

The mechanism of leukocyte and stem migration into sites of inflammation is fundamental to all inflammatory diseases such as periodontitis of the gums and rheumatoid arthritis.

Chemokines are cytokines that function by stimulating leukocytes to migrate across endothelial cells and into inflamed tissues.

By understanding these mechanisms the aim is to identify which molecules to target therapeutically.

Endothelial cells and leukocytes

In order for leukocytes to leave the blood they need to adhere to the luminal surface of endothelial cells, migrate across these cells, and enter tissues.

Chemokines are involved in both of these mechanisms, and exert their migratory effects on leukocytes by interacting with cell-surface chemokine receptors.

Work is focused on the mechanism by which endothelial cells transport chemokines to their luminal surfaces where they are presented to blood leukocytes on the tips of finger-like protrusions (microvilli).

Molecules such as syndecans, the Duffy antigen/receptor for chemokines (DARC) and chemokines are involved.

The role of several receptors such as CCR9 and GPR15/Bob on monocytes and macrophages, and their effects on cell migration and differentiation, is also being studied.

Mesenchymal stem cells

Mesenchymal stem cells (MSCs) have anti-inflammatory properties that make them potentially interesting cells in inflammatory diseases.

MSCs have the ability to migrate into tissues where they can reduce inflammation and enhance tissue repair. Particular receptors such as CCR3, CCR5, CXCR4, CXCR5 and CXCR6 occur on human MSCs.

These receptors are functional in MSC migration and could be used to enhance the entry and accumulation of MSCs in inflamed tissues.

Keratinocyte biology and autoimmune disease

Work involves researching the function and regulation of desmosomes and perturbation of the cell adhesion machinery and epidermal integrity by autoimmune antibodies.

A systems-level approach has been adopted to keratinocyte biology with the aim of identifying potential therapeutic targets for reinforcing keratinocyte and epidermal integrity.