A5072850380- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- Adenosine and Purinergic Signaling
- Ubiquitin and proteasome pathways
- Multiple Sclerosis Research Studies
- Tryptophan and brain disorders
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Protein Tyrosine Phosphatases
- Eosinophilic Esophagitis
- Immune cells in cancer
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Lymphoma Diagnosis and Treatment
- Asthma and respiratory diseases
- Neurogenesis and neuroplasticity mechanisms
- Reproductive System and Pregnancy
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Pharmacological Receptor Mechanisms and Effects
University of Bern
2024
Fundación Ciencia and Vida
2016-2022
Klinikum rechts der Isar
2020
Technical University of Munich
2020
As it has been established that demethylation of lysine 27 histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize inhibition may attenuate autoimmune disorders. We found in vivo administration GSK-J4, a selective inhibitor UTX, ameliorates severity experimental encephalomyelitis (EAE). In vitro experiments revealed anti-inflammatory effect GSK-J4 was exerted through an on dendritic cells (DCs), promoting tolerogenic...
Abstract Dopamine receptor D3 (DRD3) expressed on CD4+ T cells is required to promote neuroinflammation in a murine model of Parkinson’s disease. However, how DRD3 signaling affects cell–mediated immunity remains unknown. In this study, we report that TCR stimulation mouse induces expression, regardless the lineage specification. Importantly, functional analyses performed vivo using adoptive transfer OVA-specific OT-II into wild-type recipients show deficiency results attenuated...
Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 6% of FL (19/305). Another 13% (37/286) had amplification, which was associated with higher expression. lead to accelerated autocatalytic conversion from an enzymatically inactive profrom active increased substrate cleavage,...
The dual potential to promote tolerance or inflammation self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) DCs potentiates their inflammatory behaviour, favouring the development experimental autoimmune encephalomyelitis (EAE). Here we aimed decipher underlying mechanism and test its relevance multiple sclerosis (MS) patients. Our data shows DRD5-deficiency confined EAE mice resulted...
Galectin-8 (Gal-8) is a member of glycan-binding protein family that regulates the immune system, among other functions, and target antibodies in autoimmune disorders. However, its role multiple sclerosis (MS), an inflammatory disease central nervous system (CNS), remains unknown. We study consequences Gal-8 silencing on lymphocyte subpopulations development experimental encephalitis (EAE), to then assess presence clinical meaning anti-Gal-8 MS patients. Lgals8/Lac-Z knock-in mice lacking...
A number of studies have shown pharmacologic evidence indicating that stimulation type I dopamine receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and some other inflammatory disorders. Nevertheless, the lack drugs might discriminate between DRD1 DRD5 has made pharmacological distinction two receptors difficult. We previously genetic demonstrating a relevant role DRD5-signaling dendritic cells (DCs) favoring CD4+...
T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria have been described as important players driving inflammation. Recent evidence, supporting notion a functional phenotypic instability Th17 cells, has shown that differentiate into 1 regulatory (Tr1) cells during resolution Moreover, it suggested expression CD39 ectonucleotidase endows with immunosuppressive properties. However,...
Dendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from colitis mouse models bowel diseases (IBD) patients indicated that gut IBD is driven mainly by T-helper-1 (Th1) Th17 cells, suggesting an essential role for the development of IBD. Here we show GSK-J4, a selective inhibitor histone demethylase JMJD3/UTX, attenuated reducing increasing...
Background and AimsCD4+ T cells constitute central players in inflammatory bowel diseases (IBDs), driving inflammation the gut mucosa. Current evidence indicates that CCR9 integrin α4β7 are necessary sufficient to imprint colonic homing on CD4+ upon inflammation. Interestingly, dopaminergic signaling has been previously involved leukocyte homing. Despite dopamine levels strongly reduced inflamed mucosa, role of remains unknown. Here, we study how affects inflammation.MethodsGut was induced...
Inflammatory bowel diseases (IBDs) involve chronic inflammation of the gastrointestinal tract, where effector CD4+ T-cells play a central role. Thereby, recruitment into colonic mucosa represents key process in IBD. We recently found that CCR9 and DRD5 might form heteromeric complex on T-cell surface. The increase CCL25 production reduction dopamine levels associated with represent dual signal stimulating CCR9:DRD5 heteromer, which promotes lamina propria. Here, we aimed to analyse molecular...
Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation immune cells plays an important role in the physiopathology inflammatory disorders. Multiple sclerosis (MS) is disease involving CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models suggested that B play fundamental antigen-presenting (APC) re-stimulating T CNS well regulating T-cell by mean or anti-inflammatory...
Dopamine (DA) affects immune functions in healthy subjects (HS) and during disease by acting on D1-like (D1 D5) D2-like (D2, D3 D4) dopaminergic receptors (DR); however, its effects human polymorphonuclear leukocytes (PMN) are still poorly defined. We investigated DR expression PMN the ability of DA to affect cell migration reactive oxygen species (ROS) production. Experiments were performed cells from HS patients (Pts) with bacterial infections as well, acute phase after recovery. Some...
Inflammatory bowel diseases (IBD) involve chronic inflammation of the gastrointestinal tract, where effector CD4+ T-cells play a central role. Thereby, recruitment into colonic mucosa represents key process in IBD. We recently found that CCR9 and DRD5 might form heteromeric complex on T-cell surface. The increase CCL25 production reduction dopamine levels associated with represent dual signal stimulating CCR9:DRD5 heteromer, which promotes lamina propria. Here, we aimed to analysing...
Abstract JMJD3 a demethylase of lysine 27 histone H3 (H3K27) plays an important role in immune cells and inflammatory responses, thus appears as attractive target for the treatment diseases. Recently, GSK-J4, selective potent inhibitor was synthesized. We previously showed that GSK-J4 induced tolerogenic phenotype on dendritic (DCs) promoting generation stability Tregs well enhancing their suppressive function. However, underlying mechanisms remain unclear. Because acts upon DCs, we...
<h3>Background</h3> By targeted DNA sequencing of 305 diagnostic follicular lymphoma (FL) biopsies, we identified somatic mutations <i>Cathepsin S (CTSS)</i> in 8% cases (24/305), mostly clustered at Y132 (19/24) converting Y to D (16/19). Another 13% FL had <i>CTSS</i> amplifications (37/286), associated with higher expression (<i>P=</i><i>0.05</i>). CTSS is a cysteine protease that highly expressed endolysosomes antigen presenting cells and malignant B-cells. involved proteolytical...
Abstract Background: Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation adaptive and innate immune cells plays an important role in the physiopathology inflammatory disorders. Multiple sclerosis (MS) is disease involving CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models suggested that B-cells play fundamental antigen-presenting (APC) re-stimulating T-cells CNS well...
Abstract Multiple sclerosis (MS) involves a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Previous evidence has suggested that B-cells play fundamental role as antigen-presenting cells (APC) in mouse models of MS re-stimulating T-cells the CNS well regulating T-cell by mean inflammatory or anti-inflammatory cytokines. Despite an important dopaminergic regulation been previously described MS, effects signalling this pathology remains unexplored. Here...
Abstract Background . Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation adaptive and innate immune cells plays an important role in the physiopathology inflammatory disorders. Multiple sclerosis (MS) is disease involving CD4 + T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models suggested that B-cells play fundamental antigen-presenting (APC) re-stimulating T-cells CNS well...