A5086035918- Immunodeficiency and Autoimmune Disorders
- Adenosine and Purinergic Signaling
- Immune Cell Function and Interaction
- Atrial Fibrillation Management and Outcomes
- Systemic Sclerosis and Related Diseases
- NF-κB Signaling Pathways
- Health Systems, Economic Evaluations, Quality of Life
- Cancer Immunotherapy and Biomarkers
- Blood disorders and treatments
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Infrared Thermography in Medicine
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Digestive system and related health
- Cystic Fibrosis Research Advances
- interferon and immune responses
- Adolescent and Pediatric Healthcare
- Dermatologic Treatments and Research
- RNA regulation and disease
- Neuroscience and Neural Engineering
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- Electrochemical sensors and biosensors
- Pediatric health and respiratory diseases
University Medical Center Freiburg
2016-2025
University of Freiburg
2017-2025
Medizinische Hochschule Hannover
2021-2024
University of Milan
2013-2024
University of Liverpool
2024
Tehran University of Medical Sciences
2022
Università della Svizzera italiana
2016-2020
Sapienza University of Rome
2002-2017
École Polytechnique Fédérale de Lausanne
2015
University of Genoa
2008-2013
Prosenescence therapy has recently emerged as a novel therapeutic approach for treating cancer. However, this concept is challenged by conflicting evidence showing that the senescence-associated secretory phenotype (SASP) of senescent tumor cells can have pro- well antitumorigenic effects. Herein, we report that, in Pten-null tumors, activation Jak2/Stat3 pathway establishes an immunosuppressive microenvironment contributes to growth and chemoresistance. Activation tumors sustained...
Extracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4(+) helper T cells upon stimulation the receptor (TCR) contributes in an autocrine manner to activation mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression p2rx7, which encodes P2X7, is part transcriptional signature immunosuppressive CD4(+)CD25(+) regulatory (T(regs)). Here, we show that P2X7 by ATP inhibits...
Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for which therapeutic options are limited. Strategies to promote intestinal tissue tolerance during aGVHD may improve patient outcomes. Using single-cell RNA sequencing, we identified lipocalin-2 (LCN2)–expressing neutrophil population in mice with aGVHD. Transfer LCN2-overexpressing neutrophils or treatment recombinant LCN2 reduced severity, whereas the...
Abstract Background Cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D) is an inborn error of immunity (IEI) caused by heterozygous mutations, and characterized immune cell infiltration into the gut other organs, leading to intestinal disease, dysregulation autoimmunity. While regulatory T-cell dysfunction remains central CTLA4-D immunopathogenesis, mechanisms driving disease severity pathology are unknown but likely involve dysbiosis. We determined whether microbiome metabolome...
Homozygous nonsense mutations in ZNF341 impair its ability to activate STAT3 transcription and thereby cause immunodeficiency.
We aimed to test the relevance of deficiency adenosine deaminase 2 (DADA2) in patients with antibody and describe clinical picture disease adulthood.We screened for DADA2 a cohort 181 or without vascular lesions using next-generation sequencing targeted Sanger sequencing. All mutations were confirmed by determining ADA2 enzymatic activity levels dried plasma spots. Clinical data laboratory values collected standardized format.Following diagnosis siblings index family, we identified 9...
The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of small intestine; deletion P2rx7, encoding for P2X7, Tfh cells results enhanced IgA secretion and binding to commensal bacteria. Here, we show that activity is important generating a diverse bacterial community gut sensing microbiota-derived extracellular ATP via promotes generation proficient ecosystem metabolic homeostasis. this study indicate play role host-microbiota...
T cell dependent secretory IgA (SIgA) generated in the Peyer's patches (PPs) of small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution and microbes led to relative tolerance host's immune system towards commensal microorganisms. ATP-gated ionotropic P2X7 receptor limits follicular helper (Tfh) cells expansion germinal center (GC) reaction PPs. Here we show transient depletion intestinal ATP can dramatically improve high-affinity...
Immunoglobulin (Ig) isotype diversification by class switch recombination (CSR) is an essential process for mounting a protective humoral immune response.Ig CSR deficiencies in humans can result from intrinsic B cell defect; however, most of these are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID).Here, we show that extracellular adenosine critically contributes to human naive IgM memory cells.In cells, coordinate stimulation receptor toll-like receptors...
Abstract The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and serine/threonine kinase, has been implicated in thymopoiesis cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant ( Trpm7 R/R ) mice, that the enzymatic activity of receptor is not essential for thymopoiesis, but required CD103 transcription gut-homing intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression intestinal epithelial...
Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is major complex, which main polypeptide-conducting channel endoplasmic reticulum membrane. SEC61A1 a target gene spliced X-box binding protein and strongly induced during plasma cell (PC) differentiation.We identified novel defect studied its pathologic mechanism 11 patients from 2 unrelated families...
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency. Patients with CVID are prone to recurrent bacterial infection due failure of adequate immunoglobulin production. Monogenetic defects have been identified in approximately 25% patients. Recently, mutations IKZF1, encoding zinc-finger transcription factor IKAROS which broadly expressed hematopoietic cells, associated a CVID-like phenotype. Herein we describe eleven patients heterozygous IKZF1...
Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP virtually absent in interstitium normal tissues, it can be present hundreds micromolar range tumors, concentration compatible with activation ATP-gated ionotropic P2X7 receptor. Here, we show activity tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. stimulation affected cell cycling...
Predominantly antibody deficiencies (PAD) are a heterogeneous group of disorders characterized by dysfunctional production, low immunoglobulin levels in serum and impaired vaccine responses. The clinical picture is variable, ranging from mild symptoms to severe complications, which may include autoimmunity, gastrointestinal disease, allergy, malignancies. If left untreated, PAD patients at risk enduring disease progression, irreversible organ damage, reduced life expectancy. A timely...
Acute graft-versus-host disease causes significant mortality in patients undergoing allogeneic hematopoietic cell transplantation. Immunosuppressive treatment for can impair the beneficial graft-versus-leukemia effect and facilitate malignancy relapse. Therefore, novel approaches that protect regenerate injured tissues without impeding donor immune system are needed. Bile acids regulate multiple cellular processes close contact with intestinal epithelium, a major target of acute disease....
About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease regard to histopathology but evolves from distinct, poorly defined pathogenesis that has been linked in some cases chronic norovirus (NV) infection. Interferon-driven inflammation is prominent feature CVID it remains unknown how NV infection may contribute. Duodenal biopsies patients, stratified according the presence villous atrophy (VA), IgA plasma cells...
Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition gastrointestinal microbiota terms changing their and/or diversity. Benzyl isothiocyanate (BITC) from food and medicinal plant nasturtium (