Target T Cell Adhesion and Migration in Autoimmunity
The adhesion of T cells, and their migration into inflammatory organs, is a targeted process in the treatment of patients suffering from autoimmunity. Proper immune system function depends on directing the traffic of T cells throughout the body. Chemokines guide leukocyte homing and play a fundamental role in cellular recruitment towards the sites of inflammation.
Chemokines direct the movement of T cells from circulation into tissues. T cells in circulation roll along the endothelium until chemokine receptors are engaged leading to arrest and firm adhesion before diapedesis into the tissue. Previous therapeutic interventions into this process have focused on chemokine receptors and adhesion blockade with limited success, here we propose targeting the mediator of CXCR4 induced adhesion, PLCe1.
We have already completed a functional inhibitory RNA screen to identify signaling mediators downstream of CXCR4 within human T cells, and we have discovered a novel role for the enzyme PLCe1 in the recruitment of T cells to inflamed organs, uncovering the underlying mechanism at work. We are currently expanding these studies in order to better understand the factors leading to the recruitment and retention of auto-reactive T cells in inflamed tissues.