Abstract
Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14+ peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs). The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function.
Highlights
Dendritic cells (DCs) are major players to direct adaptive immunity or tolerance
The origins and possible subdivisions into DC subsets and the DC commonalities with macrophages (Mphs) have been discussed by numerous papers and reviews [1,2,3,4,5,6,7]. In their peripheral tissue-resident state, DCs act as immune sensors that recognize pathogens and convert into a mature or activated state enabling their migration to the draining lymph node to stimulate T cell immunity [8]
Recent data focusing on steady-state distributions of DC subsets and DC in vivo function with respect to defined cytokine deficiencies [147] or the interplay between GM-CSF, M-CSF, and IL-3 [60] may point to alternative approaches toward a better understanding of GM-CSF-derived cells
Summary
Dendritic cells (DCs) are major players to direct adaptive immunity or tolerance. More recently, the origins and possible subdivisions into DC subsets and the DC commonalities with macrophages (Mphs) have been discussed by numerous papers and reviews [1,2,3,4,5,6,7]. Protocols are available that employ Flt3L instead of GM-CSF to generate bulk populations containing mixtures of CD103+ cDCs, CD11b+ cDCs, and pDCs from mouse bone marrow [47,48,49] or but less well defined from human peripheral blood [50, 51] The generation of such DC subtypes in vitro is similar to what is observed in vivo (Figure 2). DCs expressing different levels of MHC II- and costimulatory molecules will certainly differ in transcriptional patterns belonging to the same ontogenetic DC subset [72] Such data allow further comparisons with the same maturation stages of Flt3L in vitro-generated or ex vivo-isolated cDC and pDC subsets. The treatment of bulk BM-DC cultures with different maturation stimuli appeared valuable to determine distinct response patterns by mRNA analyses, which could be attributed to DC-mediated Th1 and Th2 polarization [75]
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