A5087932335- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Adrenal Hormones and Disorders
- CAR-T cell therapy research
- Lymphatic System and Diseases
- Cell death mechanisms and regulation
- Circadian rhythm and melatonin
- Myasthenia Gravis and Thymoma
- Acute Lymphoblastic Leukemia research
- Childhood Cancer Survivors' Quality of Life
- Lymphoma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- Neonatal Respiratory Health Research
- Nerve injury and regeneration
- Immunodeficiency and Autoimmune Disorders
- Tissue Engineering and Regenerative Medicine
- Immune Response and Inflammation
- FOXO transcription factor regulation
- NF-κB Signaling Pathways
- Signaling Pathways in Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Clusterin in disease pathology
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2016-2025
Universidade do Porto
2013-2024
Instituto de Biologia Molecular e Celular
2003-2023
University of Cambridge
2017-2020
Institut de Biologie Moléculaire et Cellulaire
2018
Centro Hospitalar de Lisboa Central
2017
Health First
2017
Amsterdam UMC Location University of Amsterdam
2003-2014
Centro de Genética Clínica
2010-2014
Institut Pasteur
2008-2011
The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors self–major histocompatability complex class I (MHC-I; Ig-like [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 NK using Rag2−/−γc−/− mice transplanted with hematopoietic stem cells. Human reconstitution was intrinsically low this model because poor reactivity to mouse IL-15. Although exogenous IL-15 (hIL-15) alone made...
The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor thymopoiesis, "environmental niche" of activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice which YFP under control promoter, we identify a subset epithelial cells (TECs) that co-express high levels Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs...
Autoimmune diseases are life-threatening disorders that cause increasing disability over time. Systemic lupus erythematosus (SLE) and other autoimmune arise when immune stimuli override mechanisms of self-tolerance. Accumulating evidence has demonstrated protein glycosylation is substantially altered in disease development, but the by which glycans trigger these autoreactive responses still largely unclear. In this study, we found presence microbial-associated mannose structures at surface...
Abstract Thymic epithelial cells (TECs) help orchestrate thymopoiesis, and TEC differentiation relies on bidirectional interactions with thymocytes. Although the molecular mediators that stimulate medullary thymic cell (mTEC) maturation are partially elucidated, signals regulate cortical (cTEC) homeostasis remain elusive. Using IL-7 reporter mice, we show TECs coexpressing high levels of (Il7YFP+ TECs) reside within a subset CD205+Ly51+CD40low cTECs coexpresses Dll4, Ccl25, Ccrl1, Ctsl,...
Human naive CD8+ T cells are able to respond in an Ag-independent manner IL-7 and IL-15. Whereas largely maintains a phenotype, IL-15 drives these effector phenotype characterized, among other features, by down-regulation of the costimulatory molecule CD28. We evaluated influence CD4+ Th cell-derived common gamma-chain cytokine IL-21 on cytokine-induced cell activation. Stimulation with did not induce division only slightly increased IL-15-induced proliferation cells. Strikingly, however,...
Abstract IL-7Rα is essential for the development and homeostatic maintenance of mature T cells. Studies in humans mice have shown that expression reduced by its cognate cytokine, IL-7, Ag, suggesting active regulation IL-7 responsiveness necessary to balance cell numbers. We show IL-7- or TCR/CD28-mediated signaling induced a rapid down-regulation on naive cells mRNA protein level, with mild (10-fold) strong (50-fold) gene suppression, respectively. In both situations, was blocked...
Cytokine immunotherapies targeting T lymphocytes are attractive clinical interventions against viruses and tumors. In the mouse, homeostasis of memory α/β CD8 + cells natural killer (NK) is significantly improved with increased IL-15 bioavailability. contrast, role “transpresented” on human T-cell development in vivo unknown. We found that both CD4 immune system (HIS) mice highly sensitive to transpresented vivo, naïve (CD62L CD45RA ) phenotype − CD45RO subsets being following “boosting.”...
Apoptosis provoked by glucose shortage in dividing T cells is mediated via the BH3-only protein Noxa and inhibition of its binding partner Mcl-1. It unknown how signals from cellular metabolism can affect balance between Mcl-1 to what extent other Bcl-2 members are involved this apoptosis cascade. Here, we defined mechanism underlying relation various types metabolic stress. First, established that Noxa/Mcl-1 regulated deprivation as well general stress, changes proteasome-mediated...
Thymic epithelial cells (TECs) are the predominant intrathymic source of essential thymopoietin IL-7. Whether thymocyte-TEC interactions have a role in regulation IL-7 expression is not known. By exploiting reporter mice which yellow fluorescent protein identifies TECs expressing high levels (Il7(+) TECs), we show that Il7(+) segregate from emerging medullary during thymic organogenesis. Although normally diminish with age, found markedly retained alymphoid Rag2(-/-)Il2rg(-/-) manifest...
Cortical and medullary thymic epithelial cells (cTECs mTECs, respectively) provide inductive microenvironments for T‐cell development selection. The differentiation pathway of cTEC/mTEC lineages downstream common bipotent progenitors at discrete stages remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show the stepwise acquisition chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant cTEC differentiation. Although cTECs expressing...
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T‐cell differentiation arise from cell progenitors (TEP). However, the nature of TEPs mechanism controlling their stemness in postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that fraction cTECs generates specialized clonal‐derived colonies, which contain with sustained colony‐forming capacity ( Clono TECs). These TECs are...
Within the thymus, thymic epithelial cells (TECs) provide dedicated stroma microenvironments for T cell development. Because TEC functionality is sensitive to aging and cytoablative therapies, unraveling molecular elements that coordinate their thymopoietic role has fundamental clinical implications. Particularly, selection of CD4 depends on interactions between TCRs expressed precursors self-peptides:MHC II complexes presented by cortical TECs (cTECs). Although...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved to variants associated with milder disease. We employed the k18-hACE2 mouse model study how differences in course of infection by SARS-CoV-2 alpha, delta, and omicron relate tissue pathology immune response triggered. documented a variant-specific pattern severity, inducing discrete lung blood responses differentially impacting primary lymphoid organs. Infections alpha delta promoted bone marrow (BM) emergency...
Within the thymus, thymic epithelial cells (TECs) create dedicated microenvironments for T cell development and selection. Considering that TECs are sensitive to distinct pathophysiological conditions, uncovering molecular elements coordinate their thymopoietic role has important fundamental clinical implications. Particularly, medullary (mTECs) play a crucial in central tolerance. Our previous studies, along with others, suggest mTECs depend on factors linked genome-protecting pathways, but...
Human cytomegalovirus (hCMV) infection is characterized by a vast expansion of resting effector-type virus-specific T cells in the circulation. In mice, interleukin-7 receptor α (IL-7Rα)-expressing contain precursors for long-lived antigen-experienced CD8(+) cells, but it unclear if similar mechanisms operate to maintain these pools humans. Here, we studied whether IL-7Rα-expressing obtained from peripheral blood (PB) or lymph nodes (LNs) sustain circulating hCMV-specific pool. Using flow...