A5007972587- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Inflammasome and immune disorders
- Chronic Lymphocytic Leukemia Research
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- SARS-CoV-2 and COVID-19 Research
- Polyomavirus and related diseases
- Inflammatory Bowel Disease
- Respiratory viral infections research
- Asthma and respiratory diseases
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Plant Molecular Biology Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Long-Term Effects of COVID-19
- Atherosclerosis and Cardiovascular Diseases
- Cytomegalovirus and herpesvirus research
- Galectins and Cancer Biology
- Systemic Lupus Erythematosus Research
- Herpesvirus Infections and Treatments
- Viral-associated cancers and disorders
AstraZeneca (Brazil)
2025
AstraZeneca (Sweden)
2020-2025
National Institute of Allergy and Infectious Diseases
2018-2024
National Institutes of Health
2018-2024
National Human Genome Research Institute
2016-2022
Università della Svizzera italiana
2014-2016
Significance To design an effective subunit vaccine, it is essential to identify the most relevant protective antigen. One way achieve this goal analyze, at clonal level, human antibody response and molecules targeted by neutralizing antibodies. Here we provide example of approach in case cytomegalovirus (HCMV), a pathogen causing severe disease newborns immunosuppressed individuals. Through analysis HCMV, identified gHgLpUL128L pentamer as target potent antibodies demonstrated that vaccine...
Abstract CD4 + Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental encephalomyelitis (EAE). Here we demonstrate that priming encephalitogenic Th cells expressing RORγt T-bet producing IL-17A, IFN-γ GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence pertussis toxin (PTX) at time immunization. PTX induces early IL-1β by CD11b CCR2 Gr1 myeloid cells, which rapidly recruited antigen-draining lymph nodes. PTX-induced...
Significance In this report we identify genetic susceptibility variants for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, the most common fever syndrome in children. PFAPA shares risk loci at IL12A , STAT4, IL10 CCR1-CCR3 with Behçet’s disease recurrent defining a family of spectrum disorders. Differential HLA associations along may determine where individual phenotypes fall among
Abstract T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction are crucial for generation of robust, long-lived antibody responses, but how GC microenvironment affects Tfh is not well understood. Here we develop an in vivo cell-intrinsic CRISPR-knockout screen evaluate Th1 acute viral infection model identify regulators their physiological setting. Using a druggable-targets, alongside genetic, transcriptomic cellular analyses, function...
The integrin lymphocyte function–associated antigen 1 (LFA-1) helps to coordinate the migration, adhesion, and activation of T cells through interactions with intercellular adhesion molecule (ICAM-1) ICAM-2. LFA-1 is activated during engagement chemokine receptors cell receptor (TCR) inside-out signaling, a process that partially mediated by phosphoinositide 3-kinase (PI3K) its product phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ). To evaluate potential roles PI3K in activation, we...
Abstract Background T cell therapies are emerging as a new approach to treat and cure patients suffering from immune diseases where homeostasis is no longer maintained. For the evaluation of treatments in pre-clinical rodent models, tools required that enable fast, observer-independent high-resolution analysis different cells tissue sections. Multiplex staining samples provides valuable opportunity for comprehensive cellular dynamics with enhanced spatial resolution context compared...
Abstract Background Regulatory T cells (Treg) are a subset of CD4+ that play crucial role in maintaining immune tolerance and preventing autoimmunity. In the context Inflammatory Bowel Disease (IBD), dysregulation Treg function has been implicated pathogenesis disease. Studies have shown polyclonal potential to suppress inflammatory responses ameliorate colitis preclinical models. This led growing interest harnessing therapeutic as treatment for IBD. To support this new research effectively...
We previously reported that Cd3e-deficient mice adoptively transferred with CD4(+) T cells generate high numbers of follicular helper (Tfh) cells, which go on to induce a strong B-cell and germinal center (GC) reaction. Here, we show in this system, GC B display an altered distribution between the dark light zones, express low levels activation-induced cytidine deaminase. Furthermore, from Cd3e(-/-) accumulate fewer somatic mutations as compared wild-type mice, exhibit impaired affinity...
The SLAM family receptors contribute to diverse aspects of lymphocyte biology and signal via the small adaptor molecule SAP. Mutations affecting SAP lead X-linked lymphoproliferative syndrome Type 1, a severe immunodysregulation characterized by fulminant mononucleosis, dysgammaglobulinemia, lymphoproliferation/lymphomas. Patients mice having mutations also lack germinal centers due defect in T:B cell interactions are devoid invariant NKT (iNKT) cells. However, which how members these...
Patients with activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome (APDS) present sinopulmonary infections, lymphadenopathy, and cytomegalvirus (CMV) and/or Epstein-Barr virus (EBV) viremia, yet why patients fail to clear certain chronic viral infections remains incompletely understood. Using patient samples a mouse model (Pik3cdE1020K/+ mice), we demonstrate that, upon activation, Pik3cdE1020K/+ CD8+ T cells exhibit exaggerated features of effector populations both in vitro after...
Abstract Background Two isoforms of Phosphoinositide 3-kinase (PI3K), p110γ and p110δ, are predominantly expressed in leukocytes represent attractive therapeutic targets for the treatment allergic asthma. The study aim was to assess impact administration an inhaled PI3Kγδ inhibitor (AZD8154) a rat model Methods Firstly, we checked that tool compound, AZD8154, inhibited PI3K γ & δ kinases using cell-based assays. Subsequently, time-course conducted asthma activity lung how it is...
SARS-CoV-2 infection triggers adaptive immune responses from both T and B cells. However, most studies focus on peripheral blood, which may not fully reflect in lymphoid tissues at the site of infection. To evaluate local systemic to SARS-CoV-2, we collected tonsils, adenoids 110 children undergoing tonsillectomy/adenoidectomy during COVID-19 pandemic found 24 with evidence prior infection, including detectable neutralizing antibodies against multiple viral variants. We identified...
Phosphoinositide 3-kinase (PI3K) has 4 isoforms; two of which, p110γ and p110d, are predominantly expressed in leukocytes which represents an attractive therapeutic target for asthma. The aim this study was to assess the impact administration inhaled PI3Kγd inhibitor (AZD8154) a rat model To confirm specificity AZD8154 PI3K γ & δ kinases, cell-based assays were employed. Next, DMPK experiment performed, by dosing into airways, deduce suitable exposure profile. Subsequently, time-course...
Abstract The catalytic p110δ subunit of PI3K drives AKT pathways orchestrating activation and differentiation T B cells. Patients with gain function mutations in Pik3cd (encoding for p110δ) exhibit a primary immunodeficiency characterized by lymphopenia, lymphadenopathy, recurrent chronic infections, occasionally lymphoma. They have reduced circulating naïve increased effector cell numbers, fewer class switched memory cells inefficient responses to vaccination. Nonetheless, patient...
Abstract The p110d subunit of phosphatidylinositol-3-OH kinase (PI(3)K) is selectively expressed in leukocytes and critical for lymphocyte biology. We previously reported patients heterozygous three different germline, gain-of-function mutations PIK3CD (encoding p110d). Patients presented with sinopulmonary infections, lymphadenopathy, nodular lymphoid hyperplasia CMV and/or EBV viremia, suggestive immune dysfunction. established a mouse model (PIK3cd E1024K) that recapitulates features this...
Abstract Patients with Activated-PI3Kd Syndrome (APDS) present sinopulmonary infections, lymphadenopathy and CMV and/or EBV viremia, yet why patients fail to clear certain viral infections remains poorly understood. Using APDS patient samples a mouse model (Pik3cdE1020K/+ mice), we demonstrate that, upon activation, Pik3cdE1020K/+ CD8+ T cells exhibit exaggerated features of short-lived effectors both in vitro post-viral infection, associated increased Fas-mediated apoptosis due sustained...