Dendritic cell and macrophage heterogeneity in vivo

Abstract

Macrophage and dendritic cell (DC) are hematopoietic cells found in all tissues in the steady state that share the ability to sample the environment but have distinct function in tissue immunity. Controversies remain on the best way to distinguish macrophages from DCs in vivo. In this Perspective, we discuss how recent discoveries in the origin of the DC and macrophage lineage help establish key functional differences between tissue DC and macrophage subsets. We also emphasize the need to further understand the functional heterogeneity of the tissue DC and macrophage lineages to better comprehend the complex role of these cells in tissue homeostasis and immunity.

Figure 1. Origin of Batf3-IRF8-Id2-Dependent and -Independent Tissue-Resident DCs in Mice

Lymphoid and peripheral tissues have at least four distinct resident DC subsets: CD4⁻ CD8α⁺, CD4⁺ CD8α⁻, CD103⁺ CD11b⁻, and CD103⁻ CD11b⁺ DCs. A CD103⁺ CD11b⁺ DC subset has been best characterized within the small intestine. This figure illustrates the precursors, transcription factors (black), and cytokine receptors (red) required for the development of each population. Commitment to the mononuclear phagocyte lineage is determined at the stage of the macrophage-dendritic cell progenitor (MDP). Granulocyte/macrophage progenitor (GMP) give rise to MDP, which has lost granulocyte potential and gives rise only to monocytes and DCs restricted precursors (common DC precursors [CDPs]). CDPs have lost monocyte-macrophage differentiation potential and give rise exclusively to plasmacytoid DCs (pDCs) and pre-DCs circulating precursors that migrate to lymphoid tissues where they differentiate into lymphoid tissue CD4⁻CD8α⁺ and CD4⁺CD8α DCs and to nonlymphoid tissue to give rise to CD103⁺CD11b⁻ DCs and CD103⁺CD11b⁺ DCs. Flt3 controls myeloid precursors commitment to the DC lineage as well as the differentiation of mature DCs in tissue. The transcription factors Batf3 Id2 and IRF8 control the differentiation of lymphoid tissue CD8⁺ DC and nonlymphoid tissues CD103⁺CD11b⁻ DC but do not control CD11b⁺ DC differentiation in lymphoid and nonlymphoid tissues.