Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to initiate primary immune responses. Dendritic cells have a remarkable pattern of differentiation (maturation) that exhibits highly specific mechanisms to control antigen presentation restricted by major histocompatibility complex (MHC). MHC class I molecules present to CD8(+) cytotoxic T cells peptides that are derived mostly from cytosolic proteins, which are ubiquitinated and then degraded by the proteasome. Here we show that on inflammatory stimulation, DCs accumulate newly synthesized ubiquitinated proteins in large cytosolic structures. These structures are similar to, but distinct from, aggresomes and inclusion bodies observed in many amyloid diseases. Notably, these dendritic cell aggresome-like induced structures (DALIS) are transient, require continuous protein synthesis and do not affect the ubiquitin-proteasome pathway. Our observations suggest the existence of an organized prioritization of protein degradation in stimulated DCs, which is probably important for regulating MHC class I presentation during maturation.
Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC).Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin ؊/؊ mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin ؊/؊ mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin ؊/؊ LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin ؊/؊ mice were not impaired in their capacity to process native OVA protein for I- Dendritic cells (DC) are the most potent leukocytes to mediate the rapid initiation of a primary immune response (7). DC are bone marrow-derived leukocytes, localized in most tissues including primary and secondary lymphoid organs. In the periphery, most DC are in an immature state and are able to capture antigenic molecules via unique endocytic receptors or by fluid-phase macropinocytosis. This process generally leads to a first step of DC maturation, concomitant with their migration to secondary lymphoid organs. DC can subsequently activate naive CD4 ϩ T or CD8 ϩ T lymphocytes if peptides processed from native antigenic molecules are displayed on cell surface major histocompatibility complex (MHC) class II or I molecules in conjunction with cosignaling molecules (40).DC heterogeneity is a common feature of mice and humans. Precursor cell populations, anatomical localization, morphology, phenotype, and functions determine the type of DC. However, the origin of different DC subsets is still controversial (4). A particular subset of DC is represented by Langerhans cells (LC), which are immature DC present in the epidermis and mucosal epithelium (53, 71). LC can be generated either from myeloid precursors (77, 78) or from CD4 low lymphoid precursors (2). LC express a number of cell surface receptors including CD205/DEC205, Fc␥ and Fcε receptors, and langerin/ CD207 (70,72).Langerin is a C-type lectin oriented in a type II configuration and featuring a single carbohydrate recognition domain in its extracellular region (72). Langerin molecules oligomerize as trimers at the cell surface and display Ca 2ϩ -dependent binding specificity for mannose, N-acetyl-glucosamine, and fucose (61, 72). Langerin is a potent inducer of Birbeck granules (BG), the hallmark organelles of LC, which consist of pentalamellar and zippered membranes at the electron microscopic level (12,75). In addition to inducing BG formation, langerin is an endocytic receptor involved in the trafficking of exogenous mannosylated ligands from the cell surface into intracellular BG compartments (71).To further explore the role of langerin and BG, we generated C57BL/6 mice with a targeted disruption of the langerin gene. Although MHC class II-positive LC were detected in n...
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