- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Neuropeptides and Animal Physiology
- Migration, Health and Trauma
- Family Support in Illness
- interferon and immune responses
- Viral Infections and Vectors
- Vaccine Coverage and Hesitancy
- Heparin-Induced Thrombocytopenia and Thrombosis
- Bacteriophages and microbial interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- IL-33, ST2, and ILC Pathways
- vaccines and immunoinformatics approaches
- Sphingolipid Metabolism and Signaling
- Diabetes Management and Research
Universidade Nova de Lisboa
2015-2025
Instituto de Biologia Experimental e Tecnológica
2024-2025
Instituto Gulbenkian de Ciência
2012-2023
Nova Medical (United States)
2017
Umeå University
2003-2016
Pontifícia Universidade Católica de Minas Gerais
2012
University of Lisbon
2010
Institut Cochin
2009
Inserm
2009
Hôpital Cochin
2009
Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells not studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1(-) iNKT cell populations. We found one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population express retinoic acid receptor-related orphan receptor (gamma)t (ROR(gamma)t). These respond their ligand alpha-galactosylceramide (alpha-GalCer) vivo...
Macrophages are pivotal in mounting liver inflammatory and tissue repair responses upon hepatic injury, showing remarkable functional plasticity. The molecular mechanisms determining macrophage transition from to restorative phenotypes the damaged remain unclear. Using mouse models of acute (APAP) chronic (CCl4) drug-induced hepatotoxic injury we show that immune receptor Trem-2 controls phenotypic shifts macrophages impacts endothelial cell differentiation during recovery. gene ablation led...
Abstract While mRNA vaccines are administrated worldwide in an effort to contain the COVID-19 pandemic, heterogeneity of humoral immune response they induce at population scale remains unclear. Here, a prospective, longitudinal, cohort-study, including 1245 hospital care workers and 146 nursing home residents scheduled for BNT162b2 vaccination, together covering adult ages from 19 99 years, we analyse seroconversion SARS-CoV-2 spike protein amount spike-specific IgG, IgM IgA before 3-5 weeks...
Abstract A role for regulatory lymphocytes has been demonstrated in the pathogenesis of type 1 diabetes NOD mouse but nature these cells is debated. CD1d-restricted NKT have implicated this process. Previous reports reduced incidence mice which numbers are artificially increased attributed to enhanced production IL-4 by and a classical cells, using Vα14-Jα18 rearrangement. We now show that overexpression TCR Vα3.2+Vβ9+ producing high levels IFN-γ low amounts leads prevention diabetes,...
Invariant natural killer T (iNKT) cells constitute a distinct subset of lymphocytes exhibiting important immune-regulatory functions. Although various steps their differentiation have been well characterized, the factors controlling development remain poorly documented. Here, we show that TGF-β controls program iNKT cells. We demonstrate signaling carefully and specifically orchestrates several cell development. In vivo, this multifaceted role involves concerted action different pathways...
Serological assays are valuable tools to study SARS-CoV-2 spread and, importantly, identify individuals that were already infected and would be potentially immune a virus reinfection. Spike protein its receptor binding domain (RBD) the antigens with higher potential develop serological assays. Moreover, structural studies of these key understand molecular basis for interaction angiotensin converting enzyme 2 receptor, hopefully enabling development COVID-19 therapeutics. Thus, it is urgent...
Cerebral malaria (CM) is a life-threatening form of Plasmodium falciparum infection caused by brain inflammation. Brain endothelium dysfunction hallmark CM pathology, which also associated with the activation type I interferon (IFN) inflammatory pathway. The molecular triggers and sensors eliciting IFN cellular responses during remain largely unknown. We herein identified stimulator response cGAMP interactor 1 (STING1) as key innate immune sensor that induces Ifnβ1 transcription in mice...
The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as players disease induction, role B not clearly understood. this study we characterize different subpopulations demonstrate that marginal zone (MZ) expanded 2- 3-fold mice compared with nondiabetic C57BL/6 (B6) mice. MZ displayed a normal surface marker profile...
We used complex hypervariable repeats to evaluate the genetic diversity and structure of Prochilodus costatus (Characiformes), an ecologically economically important species endemic São Francisco River basin.Hydroelectric dams along river have led population fragmentation, which can limit gene flow.Restocking from hatcheries has been repopulate declining populations.To determine how fragmentation hatchery supplementation affect P. structure, we studied populations three sites up downstream...
Type 1 diabetes in the nonobese diabetic (NOD) mouse is a multifactorial and polygenic disease. The NOD-derived genetic factors that contribute to type are named Idd (insulin-dependent diabetes) loci. To date, biological functions of majority loci remain unknown. We have previously reported resistance NOD immature thymocytes depletion by dexamethazone (Dxm) maps Idd6 locus. Herein, we refine this phenotype using time-course experiment apoptosis induction upon Dxm treatment. confirm region...
Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), or CD152, is a negative regulator of T-cell activation and has been shown to be associated with autoimmune diseases. Previous work demonstrated defect in the expression this molecule nonobese diabetic (NOD) mice upon anti-CD3 stimulation vitro. Using genetic approach we here demonstrate that novel locus (Ctex) telomeric on chromosome 1 together Idd3 (Il-2) gene confers optimal CTLA-4 CD3 T-cells. Based these data, provide model for how...
Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic (N-IF) mouse. In liver, N-IF mouse displays particularly evident around portal tracts central veins accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly macrophages, granulocytes, eosinophils, mast cells. This inflammatory syndrome is mediated by transgenic population natural killer T...
ABSTRACT BACKGROUND While mRNA vaccines authorized for emergency use are administrated worldwide in an effort to contain the COVID-19 pandemic, little is known about heterogeneity of humoral immune response they induce at population scale. METHODS We conducted a prospective observational longitudinal study 1245 hospital care workers and 146 nursing home residents, together covering adult ages from 19 99 years. Blood samples were taken before vaccination, 3-5 weeks after first vaccine dose, 3...
Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. Objective: This work aimed evaluating HD patients immunogenicity of BTN162b2 after two doses induction phase, persistence specific antibodies along time, factors predicting these outcomes. Methods: We performed a prospective, 6-month long longitudinal cohort analysis 156 scheduled receive BTN162b2. ELISA quantified...
Dipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition DPP-4 widely used to improve glycemic control through regulation the incretin effect. Colaterally, CD26/DPP-4 appears be beneficial many inflammatory conditions, namely delaying progression liver pathology. Nevertheless, exact implications enzymatic activity dysfunction remain unclear. In this work, we investigated involvement...
Abstract Aims/hypothesis Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting and/or tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a proven molecular target diabetes-controlling drugs but the DPP4 gene control dysglycaemia not proven. Methods We dissected genetic post-OGTT and insulin release responses by Portuguese population-based cohort mainly European ancestry...
The nonobese diabetic mouse (NOD) is widely used as a model to study human type 1 diabetes (T1D). In the NOD T1D T cell-mediated autoimmune disease of complex etiology in which B cells play an essential role. One major unresolved issues genetic and/or environmental factors that trigger reaction. mouse, humans, auto-antibodies pancreatic islets are present at early ages and highly correlated progression, but their etiological role has long been disputed. have characteristics natural...