From plasmacytoid to dendritic cell: Morphological and functional switches during plasmacytoid pre‐dendritic cell differentiation

Abstract

Plasmacytoid dendritic cell precursors (pDC/IPC) are the major producers of type I interferon and have the unique ability to link innate and adaptive immunity. After producing large amounts of type I IFN in response to microbial stimulation, they can differentiate into DC capable of stimulating naive T cells and modulate the adaptive immune response. In this review, we focus on the transition between these two highly specialized cell types, which is accompanied by major morphological, structural and functional changes, many of which remain to be fully characterized. We propose that the plasmacytoid and dendritic morphologies correspond to distinct differentiation states and effector functions. IntroductionCell differentiation is defined as the progressive restriction of a cell's developmental potential and increasing specialization of its function, ultimately leading to the formation of specialized cells, tissues, and organs. During differentiation, the morphology and function of the cell evolve simultaneously, such that the cells go from being round and undifferentiated to being specialized effector cells with a specific morphology, as illustrated by hematopoiesis [1]. When a cell type reaches its highest degree of specialization, it can be called "professional", indicating that it can accomplish a certain function better than any other cell type. At this stage, it is completely dedicated to its function and cannot differentiate further. Plasmacytoid dendritic cell precursors (pDC), however, appear to be an exception. Initially described as cells with a plasma cell-like morphology located in the T cell zone of secondary lymphoid tissues but lacking markers for B or T cells [2,3], two major functional features of plasmacytoid cells have been described over the past few years [4, 5]: (i) they are professional type I IFN-producing cells (IPC), and (ii) they can further differentiate into typical DC capable of stimulating naive T cells in an antigen-specific manner. Although plasmacytoid-derived DC have some specific properties in terms of antigen uptake, processing and presentation to T cells, which will be discussed, they share with other subsets the basic defining features of DC.In this review, we will focus on the relationship between the morphology, differentiation state, and Morphology and function in cell differentiationAs a cell differentiates, morphological changes occur that are tightly associated with the acquisition of specialized functions. Early-stage non-differentiated cells are round and have a large nucleus, active chromatin, and a high nucleo-cytoplasmic ratio. They can actively proliferate but are devoid of any effector function. Their differentiated counterparts progressively acquire specific morphological features that have evolved to optimize the function of the cell. For example, the long dendrites of a neuron are key to the formation of complex cellular networks in the central nervous system [6], whereas the morphology of a muscle cell has evolved to optimize its contractile potential. Such...

Dendritic Cells in the Kidney

“…19 Under intravital and confo-cal microscopy from the capsule to the papilla of kidneys in CX 3 CR1 GFP/ϩ mice, stellate-shaped myeloid rDC form a contiguous network throughout the entire interstitium, encasing all nephrons. 19 Confirming previous studies, 6,7 myeloid rDC that resemble pre-DC (analogous to the globular shape of resident preplasmacytoid DC 15 ) are also present at low density within the mesangium of CX 3 CR1 GFP/ϩ mice. 19 Importantly, recent studies indicated that a similar anatomic surveillance network of rDC exists throughout the interstitium and mesangium of normal human kidneys.…”

“…Several functional subsets of DC have now been phenotyped, [13][14][15][16][17][18] and some of these subsets have been identified in the kidney using defined markers (Table 1). Within normal mouse kidneys, Ͼ90 to 95% of CD11c ϩ rDC are negative for CD8␣ and CD45RA (B220), 10,12,19 indicating that the majority of mouse rDC are of the myeloid lineage and major constituents of the mononuclear phagocyte system within the kidney.…”

“…[13][14][15][16][17][18] Because of the plasticity of FLT3 ϩ common myeloid and common lymphoid DC precursors to generate all DC subsets, 16 local trophic cues rather than the availability of DC precursors probably determine the constituency of rDC at steady state. Notably, although administration of the ligand for FLT3 to mice can mobilize rDC precursors and transiently increase the total number of rDC, as it does for DC in other tissues, 36 the proportion of each rDC subset is not significantly altered when compared with the normal steady state.…”

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…production of type I IFN and DCs differentiation [13], is associated with distinct morphological and structural changes, as well as a shift of the transcriptional machinery [14,15]. In particular, as PDCs differentiate to DCs they lose the capacity to produce type I IFN and upregulate MHC class I and II and the T-cell costimulatory molecules CD40, CD80 and CD86 [2,16,17].…”

Regulation of cytokine expression in human plasmacytoid dendritic cells by prostaglandin I2 analogues

“…endritic cells (DCs) are highly heterogeneous in terms of their phenotypes and function, and are known to play a major role in initiation and regulation of adaptive immune responses [1][2][3]. The seemingly diverse function of DCs is, in part, dependent on the maturation stage and nature of the stimulating antigen and, importantly, the cytokines secreted upon activation.…”