A5033895406- Reproductive System and Pregnancy
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Ectopic Pregnancy Diagnosis and Management
- Reproductive Biology and Fertility
- Immune cells in cancer
- Endometriosis Research and Treatment
- Reproductive Physiology in Livestock
- Genital Health and Disease
- Tryptophan and brain disorders
- Immunodeficiency and Autoimmune Disorders
- Celiac Disease Research and Management
- Growth Hormone and Insulin-like Growth Factors
- Renal and related cancers
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Immune Response and Inflammation
- Microscopic Colitis
- Cytokine Signaling Pathways and Interactions
- Pregnancy and Medication Impact
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Zebrafish Biomedical Research Applications
- Vitamin C and Antioxidants Research
- Adenosine and Purinergic Signaling
The San Raffaele Telethon Institute for Gene Therapy
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2025
IRCCS Ospedale San Raffaele
2021-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2014-2024
Vita-Salute San Raffaele University
2012-2015
San Raffaele University of Rome
2012
Pediatrics and Genetics
2006-2009
Federico II University Hospital
2008
Multiple mechanisms underlie the surprising willingness of mothers to tolerate semi-allogeneic fetal tissues during pregnancy. Chief among these is expression HLA-G molecules that has been largely demonstrated be responsible for reprogramming local maternal immune response towards tolerance. We recently identified a subset tolerogenic dendritic cells, DC-10 secrete high amounts IL-10 and express levels its ligand ILT4. are present in peripheral blood essential inducing adaptive regulatory T...
The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping scRNA-seq, we delineate the immune of infertile men both at semen systemic levels. We first observe that young have a pro-inflammatory milieu with increased frequency myeloid cells inflammatory mediators in seminal fluid peripheral blood, which are alterations typically observed healthy elderly men. Transcriptomic profiling confirms upregulation genes associated...
Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining role HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations 3' untranslated region locus...
In Brief Background The human regulatory macrophage (Mreg) has emerged as a promising cell type for use cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. this brief report, dehydrogenase/reductase 9 (DHRS9) is identified robust marker of Mregs. Methods cognate antigen mouse monoclonal antibody raised against Mregs was DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression within panel monocyte-derived macrophages investigated quantitative PCR,...
Abstract Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways each somatic type testes of idiopathic aplasia. We identify immaturity Leydig cells, chronic tissue inflammation, fibrosis, senescence phenotype the as well markers inflammation blood. find that deregulated expression parentally imprinted myoid immature relevant changes ratio Lamin...
During embryonic development, blood cells emerge from specialized endothelial cells, named haemogenic (HECs). As HECs are rare and only transiently found in early developing embryos, it remains difficult to distinguish them cells. Here we performed transcriptomic analysis of 28- 32-day human embryos observed that the expression Fc receptor CD32 (FCGR2B) is highly enriched cell population contains HECs. Functional analyses using pluripotent stem cell-derived revealed robust multilineage...
Celiac Disease (CD) is a T-cell mediated disorder caused by immune response to gluten, although the mechanisms underlying CD progression are still elusive. We analyzed cell composition, plasma cytokines, and gliadin-specific responses in patients with positive serology normal intestinal mucosa (potential-CD) or villous atrophy (acute-CD), after gluten-free diet (GFD). found: an inflammatory signature presence of circulating IFN-γ
Dendritic cells (DC) are antigen-presenting that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as double-edged sword since on one hand they initiate self-reactive responses the other promoting maintaining tolerance. Thus, most important either triggering self-specific or negatively auto-reactive The latter function is mediated by steady-state specialized subsets of DC, named tolerogenic DC. Clinical experimental evidence indicate prolonged...
Dendritic cells (DCs) are critically involved in inducing either immunity or tolerance. During the last decades efforts have been devoted to development of ad hoc methods manipulate DCs vitro enhance stabilize their tolerogenic properties. Addition IL-10 during monocyte-derived DC differentiation allows induction DC-10, a subset human characterized by high IL-10/IL-12 ratio and co-expression levels molecules HLA-G immunoglobulin-like transcript 4. DC-10 potent inducers adaptive type 1...
Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of 3' Un-Translated Region (UTR) HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, women unexplained Recurrent Pregnancy Loss (RPL), 2 pregnancy losses (RPL-2, n=28), or 3 more (RPL-3, n=24), and 30 a history successful Results showed RPL-2, but not RPL-3, compared to controls: i) higher frequency 14bp Ins...
Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role expression and functions Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset tolerogenic dendritic cells, DC-10 that express secrete IL-10. are present peripheral blood essential promoting maintaining tolerance via induction adaptive T regulatory (Treg) cells. We...
Mutations of the IL2RG encoding common gamma-chain (gamma(c)) lead to X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored immunological impairment in most treated patients, although lymphoproliferative events occurred five them. Even though two cases it was clearly documented an insertional mutagenesis LMO2, is conceivable that gamma(c) could have a role per se malignant lymphoproliferation. The shared cytokine receptor subunit, involved also growth...
The prominent role of dendritic cells (DC) in promoting tolerance and the development methods to generate clinical grade products allowed application tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method human DC, producing supra-physiological levels IL-10, by genetically engineering monocyte-derived with a bidirectional Lentiviral Vector (bdLV) encoding IL-10 marker gene. IL−10 are mature modulate T cell responses, promote...
Invariant Natural Killer T (iNKT) cells are a small and distinct population of crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on cell-based anti-cancer ongoing, however results not as striking murine models. Given that iNKT-based immunotherapies dependent mainly antigen-presenting (APC), tolerogenic molecule with no...
Tolerogenic dendritic cells (tolDC) play a central role in regulating immune homeostasis and promoting peripheral tolerance. These features render tolDC promising tool for cell-based approaches aimed at inducing tolerance T-cell mediated diseases allogeneic transplantation. We developed protocol to generate genetically engineered human overexpressing IL-10 (DCIL-10) by means of bidirectional lentiviral vector (LV) encoding IL-10. DCIL-10 promote allo-specific T regulatory type 1 (Tr1) cells,...
Abstract We previously reported on an X-linked SCID (X-SCID) patient, who also had peripheral growth hormone (GH) hyporesponsiveness and abnormalities of the protein phosphorylation events following GH receptor (GHR) stimulation. In present study, we examined a potential role common cytokine γ-chain (γc) in GHR signaling using EBV-transformed lymphocytes from healthy subjects γc-negative X-SCID patients. demonstrated that proliferative response to stimulation B cell lines patients was...
Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of β-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance tolerance T1D. DC-10 are subset human DCs involved IL-10-mediated tolerance. A precise monitoring the peripheral blood possible thanks discovery specific biomarkers. DC-10, being that naturally express HLA-G, may be used for appropriate staging disease. By...