Regulation of Immune Responses by Antigen Presenting Cells

Previous and current research

The Immunobiology Laboratory studies dendritic cells (DC), a type of antigen-presenting cell that regulates adaptive immunity and tolerance. Activation of DC is a pre-requisite for T cell priming. Because the immune system has evolved to combat infection, we are characterising various pathways involved in activation of murine DC by potential pathogens. One well-characterised pathway involves signalling via toll-like receptors (TLRs) but we have recently identified a novel signalling pathway involving Syk kinase that can operate independently of TLRs. Much current work is focused on addressing the role of this pathway in modulating DC function and adaptive immunity. Finally, a separate pathway involves cytosolic pattern-recognition receptors that detect hallmarks of viral presence such as RNA and promote synthesis of interferons.

DC constitute a heterogeneous family and another focus of the lab is on the role of different types of DC in the murine immune system. Although some DC subsets may be intrinsically more prone to induce Th1 or Th2 differentiation, we have shown that pattern recognition pathways can override any biases imposed by DC ontogeny. Nevertheless, we have also demonstrated that different murine DC subsets can express distinct TLR repertoires and are investigating the functional consequence of these differences. Notably, we have recently shown that selective expression of TLR3 by mouse CD8α⁺ DC allows them to become activated by dsRNA within virally-infected cells that undergo apoptosis. In addition, we have identified several gene products that can be used to distinguish different DC subtypes. The role of these proteins in DC function is being explored using genetic techniques for DC gene manipulation.

We are using several models to characterise the receptors and signalling pathways that mediate DC activation. We are examining the functional consequences of differential DC activation for immunity and tolerance. We hope that these and further studies will lead to the development of new adjuvants that can be used as tools for cancer immunotherapy.