Functions of Murine Dendritic Cells

Abstract

Dendritic cells (DCs) play critical roles in activating innate immune cells and initiating adaptive immune responses. The functions of DCs were originally obscured by their overlap with other mononuclear phagocytes, but new mouse models have allowed for the selective ablation of subsets of DCs and have helped to identify their non-redundant roles in the immune system. These tools have elucidated the functions of DCs in host defense against pathogens, autoimmunity, and cancer. This review will describe the mouse models generated to interrogate the role of DCs and will discuss how their use has progressively clarified our understanding of the unique functions of DC subsets.

Fig. 1. Functions of dendritic cell subsets in the immune response

Classical dendritic cells (cDCs) play critical roles in both innate and adaptive immunity. Furthermore, each subset of cDC appears to possess unique functions and to control the immune response against specific forms of pathogens. cDC1s control type 1 immune responses against viruses and intracellular pathogens (left panel). In these responses they prime naïve CD8 T cells, reactivate memory CD8 T cells, activate ILC1s, and induce Th1 cells. Their production of the cytokine IL-12 is vital for many of these functions. cDC1s also play a role in inducing Tregs against orally fed antigens and AIRE-dependent self-antigens expressed in the thymus, though it appears that in some cases cDC2s can also mediate Treg conversion to these antigens. Some cDC2s, on the other hand, regulate type 2 immune responses against parasites in which they induce Th2 cells (right panel). The exact mechanism by which they do this is unclear. Other cDC2s control type 3 immune responses against extracellular bacteria and fungi (right panel). In these responses, cDC2s produce IL-23 in order to activate ILC3s and to induce Th17 cells. Their production of IL-6 and TGF-β also contributes to the polarization of Th17 cells. Finally, cDC2s are also responsible for the induction of T follicular helper (Tfh) cells that regulate the germinal center response. DTR, diphtheria toxin receptor; VSV, vesicular stomatitis virus; LCMV, lymphocytic choriomeningitis virus; WNV, west nile virus; HSV, herpes simplex virus; CMV, cytomegalovirus; AIRE, autoimmune regulator; Ag, antigen.