Conditional gene deletion approaches to dissect the in vivo roles of dendritic cell subsets

Genetic engineering of mice has for many years allowed the research community to study the in vivo role of individual genes. Further, the advent of the Cre-loxP system has advanced such research to an even higher degree of sophistication by allowing us to generate mice with a conditional gene deletion in specific cell types of interest.

He will discuss his most recent research findings on two fronts. First, he will describe a recent advance in conditional gene deletion strategies developed in his lab that allows temporally-controlled deletion of a loxP-flanked target without the introduction of a Cre recombinase transgene or any other heterologous genetic material. Second, his lab is applying conditional gene deletion strategies to study the in vivo roles of specific dendritic cell subsets in T cell activation, differentiation and homeostasis. More specifically, he will show current projects about the role of vascular cell adhesion molecule-1(VCAM-1) on dendritic cells and the role of antigen presentation by so-called lymphoid dendritic cells. While intercellular adhesion molecule-1 is known to have a substantial role in T cell activation and participates in the immunological synapse, the role of VCAM-1 on dendritic cells in vivo is not known. VCAM-1 has largely been thought of as simply an adhesion molecule on blood vessels whose expression is upregulated in several inflammatory diseases. However, VCAM-1is expressed by all CD11c-positive dendritic cells in mouse spleen and lymph nodes, and at significantly higher levels on lymphoid dendritic cells than on myeloid dendritic cells. It is in this capacity that he is studying the role of VCAM-1 as well as the significance of major histocompatibility-ll-dependent antigen presentation by lymphoid dendritic cells.