Division of labor, plasticity, and crosstalk between dendritic cell subsets

Abstract

For years, dendritic cell (DC) biologists have oscillated between two seemingly antagonistic ideas: functional specialization (division of labor) of DC subsets and plasticity (multitasking). More recently, a third hypothesis is gathering support: crosstalk between functionally distinct DC subsets. This reveals a previously unappreciated hierarchy of organization within the DC system, and provides a conceptual framework to understand how cooperation between functionally distinct, yet plastic, DC subsets can shape adaptive immunity and immunological memory. Here we review the recent advances in this area.

Figure 1. Crosstalk between subsets of antigen presenting cells in the lamina propria of the intestine

Recent reports (refs. 38, 44, 45) show the existence of multiple subsets of antigen presenting cells in this microenvironment. Our recent work (ref. 38) describes the role of a unique subset of CD11b⁺ macrophages that promotes the differentiation of FoxP3⁺ regulatory T cells via secretion of IL-10 and retinoic acid (RA). These cells can also abrogate the induction of Th17 responses induced by TGF-β secreting CD11b⁺ DCs. In contrast, Belkaid et al. (ref. 44) have demonstrated that CD11b⁺CD103⁺ and CD11b⁺CD103⁻ DCs in the LP may also promote the generation of regulatory T cells via RA. In addition, Powrie et al. (ref. 45) have reported that CD103⁺ DC in the mesenteric lymph nodes can also induce regulatory T cells via RA. The relationships between the DCs subsets described by these three groups and others are at present poorly understood. Nevertheless these findings highlight mechanisms of crosstalk between DCs and macrophages in the intestine.