Alpha (v) integrins and immune regulation

Integrins are heterodimeric cell-surface adhesion molecules, essential to many cell processes. We are interested in the alpha(v) integrins, which comprise 5 family members (avb1, avb3, avb5, avb6 and avb8) and particularly in their role in phagocytosis of apoptotic cells. Mice lacking all aplha(v) integrins die at birth and so to study the role of alpha(v) in mice we have generated alpha(v) conditional knockouts using the CRE/LoxP system. Surprisingly, deleting alpha(v) in the immune system leads to spontaneous colitis and inflammation, with activation of T and B cell responses. This is due to loss of alpha(v) from Macrophages and DCs, which become unable to generate regulatory T cells and control mucosal immune responses. This work has uncovered exciting new roles for alpha(v) integrins in the control of immune responses and in future research we will try to understand the mechanisms of alpha(v) action and how this goes wrong in disease.