Abstract
Dendritic cells (DCs) are antigen-presenting cells with the unique capacity to initiate primary immune responses1. Dendritic cells have a remarkable pattern of differentiation (maturation) that exhibits highly specific mechanisms to control antigen presentation restricted by major histocompatibility complex (MHC)2. 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 proteasome3,4. 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 diseases5,6. 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.
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Acknowledgements
We thank A.-M. Imbert, C. Chabannon and all the personnel at the cell repository of the Centre de Thérapie Cellulaire (Institut Paoli-Calmettes) for providing access to human CD34+ cells. We also thank J. Yewdell, P. Machy and L. Delamarre for a gift of antibody and for discussions. This work is supported by grants to P.P. from the Ministère de la Recherche et de la Technologie (Action Concertée Initiative Blanche), the Association pour la Recherche contre le Cancer, and the Fondation Schlumberger pour l'Education et la Recherche. H.L. is supported by a Sidaction and Agence Nationale de Recherches sur la Sida fellowships, and E.G. is an EU Marie Curie fellow.
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Lelouard, H., Gatti, E., Cappello, F. et al. Transient aggregation of ubiquitinated proteins during dendritic cell maturation. Nature 417, 177–182 (2002). https://doi.org/10.1038/417177a
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DOI: https://doi.org/10.1038/417177a
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