A5014495379- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- T-cell and Retrovirus Studies
- Acute Lymphoblastic Leukemia research
- Neuroinflammation and Neurodegeneration Mechanisms
- Adrenal Hormones and Disorders
- interferon and immune responses
- Eosinophilic Esophagitis
- Single-cell and spatial transcriptomics
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Microscopic Colitis
- Cell death mechanisms and regulation
- Psoriasis: Treatment and Pathogenesis
- Italian Fascism and Post-war Society
- Atherosclerosis and Cardiovascular Diseases
- Wnt/β-catenin signaling in development and cancer
- Inflammatory Bowel Disease
University College London
2016-2025
The Royal Free Hospital
2016-2025
Institute of Infection and Immunity
2017-2025
Roland Hill (United Kingdom)
2016-2023
Instituto Gulbenkian de Ciência
2011-2023
Centro Infantil Boldrini
2011-2023
University of Lisbon
2023
Instituto de Medicina Molecular João Lobo Antunes
2023
National Institute for Medical Research
2015
Medical Research Council
1996-2014
Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise exert their within intestinal tissue. ILC-driven colitis depends production granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits maintains inflammatory monocytes....
Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (T
In addition to helper and regulatory potential, CD4
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic death (ICD). Although the catalytic function of RIPK1 is required to trigger death, its non-catalytic scaffold mediates strong pro-survival signaling. Accordingly, cancer cells can hijack block necroptosis evade immune detection. We generated small-molecule proteolysis-targeting chimera (PROTAC) selectively degraded human murine...
Previous studies have shown that autoimmune thyroiditis can be induced in normal laboratory rats after thymectomy and split dose γ-irradiation. Development of disease prevented by reconstitution PVG shortly their final irradiation with either peripheral CD4+CD45RC− T cells or CD4+CD8− thymocytes from syngeneic donors. Although the activity both populations is known to depend on activities endogenously produced interleukin 4 transforming growth factor β, implying a common mechanism, issue...
Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation PVG.RT1u rats can be prevented their reconstitution with peripheral CD4+CD45RC−TCR-α/β+RT6+ cells CD4+CD8− thymocytes from normal syngeneic donors. These data provide evidence for the role regulatory T in prevention a tissue-specific disease but mode action these has not been reported previously. In this study, thyroiditis was induced PVG.RT1c using similar protocol irradiation....
The importance of microenvironmental factors for driving progression in leukemia has been debated. Previous evidence pointed to interleukin-7 (IL-7), a fundamental cytokine normal T-cell development and homeostasis, as an important determinant the viability proliferation acute lymphoblastic (T-ALL) cells vitro. In this study, we report that IL-7 is also critical T-ALL progression. cell lines primary samples initiated more slowly when engrafted immunocompromised Rag2(-/-)IL2rg(-/-) mice...
The thymic medulla represents a key site for the induction of T cell tolerance. In particular, autoimmune regulator (Aire)-expressing medullary epithelial cells (mTECs) provide spectrum tissue-restricted Ags that, through both direct presentation and cross-presentation by dendritic cells, purge developing repertoire specificities. Despite this role, mechanisms Aire(+) mTEC development remain unclear, particularly those stages that occur post-Aire expression represent terminal...
T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of cells in thymus as well their homeostasis peripheral lymphoid organs. Here we show that pMHC contact modulates expression CD5 by naive CD4 a process requires continued p56lck. Reduced levels deprived are predictive elevated Ca2+ responses to subsequent TCR engagement anti-CD3 or nominal antigen. Adaptation may be important for regulating responsiveness.
Abstract TCR and cytokine signals induce naive T cells to undergo spontaneous divisions as part of a homeostatic response conditions cell deficiency. The under which these evoke the their interaction with each other are poorly understood, yet very important clinically in considering strategies for immune reconstitution. Here, we show that p56lck (lck)-mediated IL-7R able stimulate proliferation lymphopenic hosts independently one another, but can also synergize facilitate proliferation....
Rats of the PVG.RT1u strain develop autoimmune diabetes when thymectomized at 6 wk age and are rendered relatively lymphopenic by a cumulative dose 1,000 rads 137Cs γ-irradiation given in four split doses. Previous studies have shown that disease is prevented intravenous injection 5 × 106 CD4+ CD45RC− TCRαβ+ RT6+ peripheral T cells from normal syngeneic donors. These memory phenotype presumably primed to some extrathymic antigen. However, we now report CD8− population mature thymocytes very...
To investigate the temporal regulation of commitment immature thymocytes to either CD4(+) or CD8(+) lineage in thymus, we developed a transgenic mouse that expressed tetracycline-inducible gene encoding tyrosine kinase zeta chain-associated protein 70 kD (Zap70), which restored development Zap70(-/-) arrested at preselection, CD4(+)CD8(+) double-positive (DP) stage. After induction expression Zap70 and production protein, single-positive (SP) cells Zbtb7b (which encodes T cell-associated...
It has long been recognized that the T-cell compartment more CD4 helper than CD8 cytotoxic T cells, and this is most evident looking at development in thymus. However, it remains unknown how thymocyte so favors lineage development. To identify basis of asymmetry, we analyzed synchronized cohorts thymocytes vivo estimated rates death differentiation throughout development, inferring lineage-specific efficiencies selection. Our analysis suggested roughly equal numbers cells each enter...
Characterising the longevity of immunological memory requires establishing rules underlying renewal and death peripheral T cells. However, we lack knowledge population structure how self-renewal de novo influx contribute to maintenance compartments. Here, characterise kinetics murine CD4 cell subsets by measuring rates new cells using detailed timecourses DNA labelling that also distinguish behaviour recently divided quiescent We find both effector central comprise subpopulations with highly...
Abstract The role of TCR signals triggered by recognition self MHCs in maintaining the survival naive peripheral T cells remains controversial. Here we examine Src family kinases, p56lck (Lck) and p59fyn (Fyn), cells. We show that long term requires a combination transduced kinases through IL-7R. In absence either one, die slowly, but if both are removed, cell loss is greatly accelerated. signal can be mediated Fyn or Lck at wild-type levels expression, not alone expressed suboptimally....
Interactions between the T cell receptor (TCR) and major histocompatibility complex antigens are essential for survival homeostasis of peripheral lymphocytes. However, little is known about TCR signaling events that result from these interactions. The pool p56 lck (lck)–deficient mice was reconstituted by expression an inducible transgene. Continued naı̈ve cells observed long periods after switching off Adoptive transfer into lymphopoienic hosts confirmed independent but revealed its role in...
The developmental pathways of regulatory T cells (T(reg)) generation in the thymus are not fully understood. In this study, we reconstituted thymic development Zap70-deficient thymocytes with a tetracycline-inducible Zap70 transgene to allow temporal dissection T(reg) development. We find that develop distinctive kinetics, first appearing by day 4 among CD4 single-positive (SP) thymocytes. Accepted models CD25(+)Foxp3(+) selection suggest via CD25(+)Foxp3(-) SP precursors. contrast, our...