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Institution

Instituto de Medicina Molecular

About: Instituto de Medicina Molecular is a based out in . It is known for research contribution in the topics: Population & T cell. The organization has 1662 authors who have published 3562 publications receiving 111648 citations. The organization is also known as: iMM Lisboa - Instituto de Medicina Molecular & Instituto de Medicina Molecular João Lobo Antunes.


Papers
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Journal ArticleDOI
TL;DR: The results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.
Abstract: Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.

2,006 citations

Journal ArticleDOI
TL;DR: A group of leaders in the field define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Abstract: Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.

1,116 citations

Journal ArticleDOI
TL;DR: The results reveal a role for selected ESCRT components and accessory proteins in exosome secretion and composition by HeLa-CIITA and highlight biogenetic differences in vesicles secreted by a tumour cell line and primary DCs.
Abstract: Exosomes are extracellular vesicles (EVs) secreted upon fusion of endosomal multivesicular bodies (MVBs) with the plasma membrane. The mechanisms involved in their biogenesis have not yet been fully identified although they could be used to modulate exosome formation and therefore are a promising tool in understanding exosome functions. We have performed an RNA interference screen targeting 23 components of the endosomal sorting complex required for transport (ESCRT) machinery and associated proteins in MHC class II (MHC II)-expressing HeLa-CIITA cells. Silencing of HRS, STAM1 or TSG101 reduced the secretion of EV-associated CD63 and MHC II but each gene altered differently the size and/or protein composition of secreted EVs, as quantified by immuno-electron microscopy. By contrast, depletion of VPS4B augmented this secretion while not altering the features of EVs. For several other ESCRT subunits, it was not possible to draw any conclusions about their involvement in exosome biogenesis from the screen. Interestingly, silencing of ALIX increased MHC II exosomal secretion, as a result of an overall increase in intracellular MHC II protein and mRNA levels. In human dendritic cells (DCs), ALIX depletion also increased MHC II in the cells, but not in the released CD63-positive EVs. Such differences could be attributed to a greater heterogeneity in size, and higher MHC II and lower CD63 levels in vesicles recovered from DCs as compared with HeLa-CIITA. The results reveal a role for selected ESCRT components and accessory proteins in exosome secretion and composition by HeLa-CIITA. They also highlight biogenetic differences in vesicles secreted by a tumour cell line and primary DCs.

1,102 citations

Journal ArticleDOI
TL;DR: The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non‐motor symptoms and found that most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy.
Abstract: The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treat- ments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full

1,061 citations

Journal ArticleDOI
TL;DR: This poster presents a meta-modelling procedure called “spot-spot analysis” that allows for the direct comparison of the response of the immune system to various types of carbohydrates and its role in disease.

955 citations


Authors

Showing all 1662 results

NameH-indexPapersCitations
Scott L. Friedman12648862931
Helena Santos114105854286
Nuno C. Santos11488547038
José M. Ferro8341730984
Michael Swash8257331000
Pedro Marques-Vidal8059148141
Gabriel Waksman7823121143
Tiago F. Outeiro6630519589
Maria Carmo-Fonseca6519613669
Cristina Sampaio6316520564
Dimitris Kioussis6114512373
Yannick Béjot5733133027
Joaquim J. Ferreira5640913044
Ana M. Sebastião5423510285
Ruy M. Ribeiro531808957
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20224
2021406
2020430
2019343
2018308
2017327