Development, Diversity, and Function of Dendritic Cells in Mouse and Human

Abstract

The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs). pDCs are potent producers of type I interferons and thus these cells are implicated in immune responses that depend on this cytokine. Mouse models deficient in the cDC1 lineage have revealed their importance in directing immune responses to intracellular bacteria, viruses, and cancer through the cross-presentation of cell-associated antigen. Models of transcription factor deficiency have been used to identify subsets of cDC2 that are required for T helper (Th)2 and Th17 responses to certain pathogens; however, no single factor is known to be absolutely required for the development of the complete cDC2 lineage. In this review, we will discuss the current state of knowledge of mouse and human DC development and function and highlight areas in the field that remain unresolved.

The MYCL and MXD1 transcription factors regulate the fitness of murine dendritic cells

“…Recent whole-transcriptome analyses of DCs during homeostatic and inflammatory maturation found suppression of Mycl, suggesting that its expression is most likely limited to immature cDCs (25,26). Thus, we examined Mycl-GFP expression in Mycl gfp/+ mice, using CCR7 expression as a canonical marker of maturation status of DCs in peripheral lymphoid organs (28 confirming that Mycl expression is suppressed on maturation in this tissue ( Fig. 1 A and B).…”

“…It is widely accepted that DC maturation correlates with the capacity of DCs to effectively regulate immune responses (28). The present study reveals mechanisms by which MYCL and MXD1 regulate cellular fitness in a primary cell lineage.…”

Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

“…The GCN analysis did identify three separate DC-associated co-expression clusters that are consistent with current knowledge of putative DC subsets and adaptation in mice [20,21,106]. Cluster 13 includes Ccr7 and transcription factors Spib and Stat4, Cluster 28 includes Flt3, Kit and the transcription factor Relb and Cluster 49 includes cDC1 markers Itgae (CD103) and Xcr1.…”

Maintenance of tight junction barrier integrity in cell turnover and skin diseases

“…Immunofluorescence and paracellular permeation studies of normal human trunk skin, mouse ear, abdominal skin and back skin revealed that only a single layer of cells, the SG2 cell layer, is equipped with TJs that limits paracellular molecular movement and divides cell membrane into apical and basolateral membrane. [4,7,25,35] In the immunofluorescent studies using vertical sections of the skin, TJ-forming cell should be determined by the combination of three characteristics shown below. [7] One is the localization of ZO-1 or occludin at the apical edge of the lateral cell-cell contact.…”