16 results on '"Gatti E"'
Search Results
2. Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow
- Author
-
Saino, N, Ambrosini, R, Albetti, B, Caprioli, M, De Giorgio, B, Gatti, E, Liechti, F, Parolini, M, Romano, A, Romano, M, Scandolara, C, Gianfranceschi, L, Bollati, V, Rubolini, D, Rubolini, D., Saino, N, Ambrosini, R, Albetti, B, Caprioli, M, De Giorgio, B, Gatti, E, Liechti, F, Parolini, M, Romano, A, Romano, M, Scandolara, C, Gianfranceschi, L, Bollati, V, Rubolini, D, and Rubolini, D.
- Abstract
Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.
- Published
- 2017
3. MARCH9-mediated ubiquitination regulates MHC i export from the TGN
- Author
-
De Angelis Rigotti, F., De Gassart, A., Pforr, Christof, Cano, F., N'Guessan, P., Combes, A., Camossetto, V., Lehner, P., Pierre, P., Gatti, E., De Angelis Rigotti, F., De Gassart, A., Pforr, Christof, Cano, F., N'Guessan, P., Combes, A., Camossetto, V., Lehner, P., Pierre, P., and Gatti, E.
- Abstract
© 2017 Australasian Society for Immunology Inc. All rights reserved. Given the heterogeneous nature of antigens, major histocompatibility complex class I (MHC I) intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC I delivery to the plasma membrane. We show here that MHC I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues. MHC I ubiquitination is mediated by the E3 ligase membrane-associated RING-CH 9 (MARCH9) and allows MHC I access to Syntaxin 6-positive endosomal compartments. We further show that MARCH9 can also target the human MHC I-like lipid antigen-presentation molecule CD1a. MARCH9 expression is modulated by microbial pattern exposure in dendritic cells (DCs), thus revealing the role of this ubiquitin E3 ligase in coordinating MHC I access to endosomes and DC activation for efficient antigen cross-presentation.
- Published
- 2017
4. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells
- Author
-
Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Crippa, M., Valtorta, Silvia, MORESCO, ROSA MARIA, Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Crippa, M., Valtorta, Silvia, and MORESCO, ROSA MARIA
- Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment.
- Published
- 2016
5. Clock gene polymorphism and scheduling of migration: A geolocator study of the barn swallow Hirundo rustica
- Author
-
Bazzi, G, Ambrosini, R, Caprioli, M, Costanzo, A, Liechti, F, Gatti, E, Gianfranceschi, L, Podofillini, S, Romano, A, Romano, M, Scandolara, C, Saino, N, Rubolini, D, Rubolini, D., AMBROSINI, ROBERTO, Bazzi, G, Ambrosini, R, Caprioli, M, Costanzo, A, Liechti, F, Gatti, E, Gianfranceschi, L, Podofillini, S, Romano, A, Romano, M, Scandolara, C, Saino, N, Rubolini, D, Rubolini, D., and AMBROSINI, ROBERTO
- Abstract
Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving 'clock' genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds.
- Published
- 2015
6. Clinical effects of a dietary fibre supplement: a review
- Author
-
Gatti, E.
- Subjects
Fiber in human nutrition -- Evaluation ,Diet therapy -- Analysis ,Constipation -- Care and treatment - Abstract
Colonic and metabolic effects due to the dietary fibre addition can be used therapeutically in many clinical situations. The clinical study of dietary fibre supplementation is done in constipation, body weight reduction and blood pressure. Some fibers such as bran and ispaghula generates larger and softer stools, which are useful in treating constipation.
- Published
- 1995
7. Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow
- Author
-
Valentina Bollati, Diego Rubolini, Benedetta Albetti, Felix Liechti, Emanuele Gatti, Manuela Caprioli, Roberto Ambrosini, Nicola Saino, Andrea Romano, Luca Gianfranceschi, Barbara De Giorgio, Chiara Scandolara, Maria Romano, Marco Parolini, Saino, N, Ambrosini, R, Albetti, B, Caprioli, M, De Giorgio, B, Gatti, E, Liechti, F, Parolini, M, Romano, A, Romano, M, Scandolara, C, Gianfranceschi, L, Bollati, V, and Rubolini, D
- Subjects
0106 biological sciences ,0301 basic medicine ,Candidate gene ,Population ,CLOCK Proteins ,010603 evolutionary biology ,01 natural sciences ,Article ,Epigenesis, Genetic ,Sexual Behavior, Animal ,03 medical and health sciences ,Hirundo ,Animals ,Epigenetics ,education ,education.field_of_study ,Multidisciplinary ,biology ,Phenology ,Ecology ,Methylation ,DNA Methylation ,biology.organism_classification ,CLOCK ,Phenotype ,030104 developmental biology ,Swallows ,Evolutionary biology ,DNA methylation ,Animal Migration ,BIO/07 - ECOLOGIA - Abstract
Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.
- Published
- 2017
- Full Text
- View/download PDF
8. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells
- Author
-
Hilda de Vries, Roberta Frapolli, Elena Gatti, Camilla Recordati, Michela Frenquelli, Maurizio D'Incalci, Marco Bianchi, Massimo Venturini, Antonello E. Spinelli, Francesco De Marchis, Luca Crippa, Renzo Boldorini, Eltjona Rrapaj, Rosanna Mezzapelle, Eugenio Scanziani, Claudio Doglioni, Massimo P. Crippa, Chiara Ceriotti, Laura Perani, Silvia Valtorta, Lorenza Pecciarini, Alessandro Preti, Rosa Maria Moresco, Anton Berns, Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Spinelli, Ae, Moresco, Rm, Doglioni, Claudio, de Vries, H, D’Incalci, M, Bianchi, MARCO EMILIO, and Crippa, Mp
- Subjects
Mesothelioma ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Antineoplastic Agents ,Pemetrexed ,HMGB1 ,Deoxycytidine ,Article ,Proinflammatory cytokine ,BALB/c ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Malignant Mesotheliom ,Cell Line, Tumor ,medicine ,Mesothelioma, HMGB1, in vivo, imaging ,cancer ,Animals ,Humans ,HMGB1 Protein ,Cisplatin ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,business.industry ,Mesothelioma, Malignant ,biology.organism_classification ,medicine.disease ,Survival Analysis ,Gemcitabine ,030104 developmental biology ,Cell culture ,mesothelioma ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,Immunocompetence ,Neoplasm Transplantation ,medicine.drug - Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment. Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment
- Published
- 2016
- Full Text
- View/download PDF
9. Physico-chemical properties and toxicological effects on plant and algal models of carbon nanosheets from a nettle fibre clone.
- Author
-
Shah SS, Qasem MAA, Berni R, Del Casino C, Cai G, Contal S, Ahmad I, Siddiqui KS, Gatti E, Predieri S, Hausman JF, Cambier S, Guerriero G, and Aziz MA
- Subjects
- Microalgae, Nicotiana, Toxicity Tests, Carbon toxicity, Nanostructures toxicity, Urtica dioica
- Abstract
Carbon nanosheets are two-dimensional nanostructured materials that have applications as energy storage devices, electrochemical sensors, sample supports, filtration membranes, thanks to their high porosity and surface area. Here, for the first time, carbon nanosheets have been prepared from the stems and leaves of a nettle fibre clone, by using a cheap and straight-forward procedure that can be easily scaled up. The nanomaterial shows interesting physical parameters, namely interconnectivity of pores, graphitization, surface area and pore width. These characteristics are similar to those described for the nanomaterials obtained from other fibre crops. However, the advantage of nettle over other plants is its fast growth and easy propagation of homogeneous material using stem cuttings. This last aspect guarantees homogeneity of the starting raw material, a feature that is sought-after to get a nanomaterial with homogeneous and reproducible properties. To evaluate the potential toxic effects if released in the environment, an assessment of the impact on plant reproduction performance and microalgal growth has been carried out by using tobacco pollen cells and the green microalga Pseudokirchneriella subcapitata. No inhibitory effects on pollen germination are recorded, while algal growth inhibition is observed at higher concentrations of leaf carbon nanosheets with lower graphitization degree.
- Published
- 2021
- Full Text
- View/download PDF
10. Emotional ratings and skin conductance response to visual, auditory and haptic stimuli.
- Author
-
Gatti E, Calzolari E, Maggioni E, and Obrist M
- Subjects
- Acoustic Stimulation, Female, Humans, Male, Visual Perception, Emotions, Galvanic Skin Response
- Abstract
The human emotional reactions to stimuli delivered by different sensory modalities is a topic of interest for many disciplines, from Human-Computer-Interaction to cognitive sciences. Different databases of stimuli eliciting emotional reaction are available, tested on a high number of participants. Interestingly, stimuli within one database are always of the same type. In other words, to date, no data was obtained and compared from distinct types of emotion-eliciting stimuli from the same participant. This makes it difficult to use different databases within the same experiment, limiting the complexity of experiments investigating emotional reactions. Moreover, whereas the stimuli and the participants' rating to the stimuli are available, physiological reactions of participants to the emotional stimuli are often recorded but not shared. Here, we test stimuli delivered either through a visual, auditory, or haptic modality in a within participant experimental design. We provide the results of our study in the form of a MATLAB structure including basic demographics on the participants, the participant's self-assessment of his/her emotional state, and his/her physiological reactions (i.e., skin conductance).
- Published
- 2018
- Full Text
- View/download PDF
11. Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow.
- Author
-
Saino N, Ambrosini R, Albetti B, Caprioli M, De Giorgio B, Gatti E, Liechti F, Parolini M, Romano A, Romano M, Scandolara C, Gianfranceschi L, Bollati V, and Rubolini D
- Subjects
- Animals, DNA Methylation, Animal Migration, CLOCK Proteins genetics, Epigenesis, Genetic, Phenotype, Sexual Behavior, Animal, Swallows genetics, Swallows physiology
- Abstract
Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5'-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.
- Published
- 2017
- Full Text
- View/download PDF
12. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells.
- Author
-
Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, Spinelli AE, Perani L, Venturini M, Valtorta S, Moresco RM, Pecciarini L, Doglioni C, Frenquelli M, Crippa L, Recordati C, Scanziani E, de Vries H, Berns A, Frapolli R, Boldorini R, D'Incalci M, Bianchi ME, and Crippa MP
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Cell Line, Tumor, Cisplatin therapeutic use, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Female, HMGB1 Protein metabolism, Humans, Immunocompetence, Mesothelioma, Malignant, Mice, Inbred BALB C, Neoplasm Transplantation, Pemetrexed therapeutic use, Survival Analysis, Gemcitabine, Lung Neoplasms blood supply, Lung Neoplasms drug therapy, Lung Neoplasms immunology, Lung Neoplasms pathology, Mesothelioma blood supply, Mesothelioma drug therapy, Mesothelioma immunology, Mesothelioma pathology
- Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment.
- Published
- 2016
- Full Text
- View/download PDF
13. Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica.
- Author
-
Bazzi G, Ambrosini R, Caprioli M, Costanzo A, Liechti F, Gatti E, Gianfranceschi L, Podofillini S, Romano A, Romano M, Scandolara C, Saino N, and Rubolini D
- Subjects
- Alleles, Animals, Female, Genotype, Italy, Male, Reproduction genetics, Seasons, Switzerland, Animal Migration physiology, CLOCK Proteins genetics, Circadian Rhythm genetics, Polymorphism, Genetic genetics, Swallows genetics
- Abstract
Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving 'clock' genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds.
- Published
- 2015
- Full Text
- View/download PDF
14. Suppression of eIF2α kinases alleviates Alzheimer's disease-related plasticity and memory deficits.
- Author
-
Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, Cavener DR, and Klann E
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease genetics, Alzheimer Disease therapy, Amyloid beta-Protein Precursor genetics, Animals, Anisomycin pharmacology, Anisomycin therapeutic use, Disease Models, Animal, Female, Hippocampus pathology, Humans, In Vitro Techniques, Male, Maze Learning drug effects, Maze Learning physiology, Memory Disorders metabolism, Memory Disorders therapy, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation genetics, Neuronal Plasticity physiology, Presenilin-1 genetics, Protein Synthesis Inhibitors pharmacology, Protein Synthesis Inhibitors therapeutic use, Recognition, Psychology drug effects, Recognition, Psychology physiology, eIF-2 Kinase genetics, Alzheimer Disease complications, Alzheimer Disease pathology, Memory Disorders etiology, Neuronal Plasticity genetics, eIF-2 Kinase metabolism
- Abstract
Expression of long-lasting synaptic plasticity and long-term memory requires protein synthesis, which can be repressed by phosphorylation of eukaryotic initiation factor 2 α-subunit (eIF2α). Elevated phosphorylation of eIF2α has been observed in the brains of Alzheimer's disease patients and Alzheimer's disease model mice. Therefore, we tested whether suppressing eIF2α kinases could alleviate synaptic plasticity and memory deficits in Alzheimer's disease model mice. Genetic deletion of eIF2α kinase PERK prevented enhanced phosphorylation of eIF2α and deficits in protein synthesis, synaptic plasticity and spatial memory in mice that express familial Alzheimer's disease-related mutations in APP and PSEN1. Similarly, deletion of another eIF2α kinase, GCN2, prevented impairments of synaptic plasticity and defects in spatial memory exhibited by the Alzheimer's disease model mice. Our findings implicate aberrant eIF2α phosphorylation as a previously unidentified molecular mechanism underlying Alzheimer's disease-related synaptic pathophysioloy and memory dysfunction and suggest that PERK and GCN2 are potential therapeutic targets for treatment of individuals with Alzheimer's disease.
- Published
- 2013
- Full Text
- View/download PDF
15. Transient aggregation of ubiquitinated proteins during dendritic cell maturation.
- Author
-
Lelouard H, Gatti E, Cappello F, Gresser O, Camosseto V, and Pierre P
- Subjects
- Animals, Antigen Presentation, Canavanine pharmacology, Catalytic Domain, Cysteine Endopeptidases chemistry, Cysteine Endopeptidases metabolism, Cytoplasm metabolism, Dendritic Cells drug effects, Dendritic Cells immunology, Histocompatibility Antigens Class I biosynthesis, Histocompatibility Antigens Class I immunology, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred C57BL, Multienzyme Complexes chemistry, Multienzyme Complexes metabolism, Nocodazole pharmacology, Oligopeptides pharmacology, Proteasome Endopeptidase Complex, Protein Binding drug effects, Protein Biosynthesis, Protein Denaturation, Protein Subunits, Protein Transport drug effects, Cell Differentiation drug effects, Dendritic Cells cytology, Dendritic Cells metabolism, Histocompatibility Antigens Class I metabolism, Ubiquitin metabolism
- Abstract
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.
- Published
- 2002
- Full Text
- View/download PDF
16. Developmental regulation of MHC class II transport in mouse dendritic cells.
- Author
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Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, and Mellman I
- Subjects
- Amino Acid Sequence, Animals, Antigen Presentation, B-Lymphocytes immunology, Biological Transport, Bone Marrow Cells, Cell Differentiation, Cell Line, Cell Membrane metabolism, Cells, Cultured, Dendritic Cells cytology, Dendritic Cells immunology, Islets of Langerhans cytology, Lysosomes metabolism, Male, Mice, Molecular Sequence Data, Phenotype, Dendritic Cells metabolism, Histocompatibility Antigens Class II metabolism
- Abstract
Dendritic cells (DCs) have the unique capacity to initiate primary and secondary immune responses. They acquire antigens in peripheral tissues and migrate to lymphoid organs where they present processed peptides to T cells. DCs must therefore exist in distinct functional states, an idea that is supported by observations that they downregulate endocytosis and upregulate surface molecules of the class II major histocompatibility complex (MHC) upon maturation. Here we investigate the features of DC maturation by reconstituting the terminal differentiation of mouse DCs in vitro and in situ. We find that early DCs, corresponding to those found in peripheral tissues, exhibit a phenotype in which most class II molecules are intracellular and localized to lysosomes. Upon maturation, these cells give rise to a new intermediate phenotype in which intracellular class II molecules are found in peripheral non-lysosomal vesicles, similar to the specialized CIIV population seen in B cells. The intermediate cells then differentiate into late DCs which express almost all of their class II molecules on the plasma membrane. These variations in class II compartmentalization are accompanied by dramatic alterations in the intracellular transport of the new class II molecules and in antigen presentation. We found that although early DCs could not present antigen immediately after uptake, efficient presentation of the previously internalized antigen occurred after maturation, 24-48 hours later. By regulating class II transport and compartmentalization, DCs are able to delay antigen display, a property crucial to their role in immune surveillance.
- Published
- 1997
- Full Text
- View/download PDF
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