Clarifi cation of dendritic cell subset functions based on the gene-manipulated mice

Abstract

Dendritic cells (DCs) are professional antigen presenting cells involved not only in provoking innate immune responses but also in establishing adaptive immune responses. In order to clarify the critical in vivo roles of DCs, generation of gene-manipulated mice for DC ablation is very useful. DCs are heterogeneous and consist of various subsets, including plasmacytoid DCs (pDCs) or conventional DCs (cDCs). These DC subsets show the subset-specific functions. We have recently generated the mutant mice in which CD103⁺CD11b^- cDCs can be selectively ablated. The system is based on the selective expression of a chemokine receptor, XCR1, in the DC subset. CD103⁺CD11b^- cDCs are known for their high ability to incorporate dying cells and crosspresent the antigens to generate cytotoxic T cells. These functions are critical for protective responses against viral infection or tumors, but additional roles of the DC subset are largely unknown. By using our mutant mice, critical in vivo roles of the DC subset have been clarified. Our mutant mice are superior to the mutant mice generated so far in terms of the selectivity of the cell ablation and marking. Therefore, the mice should contribute to the clarification of additional roles of the DC subset. The DC subset is present also in the human. So the knowledge based on the mutant mice can be applicable to the human system.