A5049796940- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Response and Inflammation
- Pediatric health and respiratory diseases
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Allergic Rhinitis and Sensitization
- Asthma and respiratory diseases
- Virus-based gene therapy research
- Bacillus and Francisella bacterial research
- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- HIV Research and Treatment
- Chemokine receptors and signaling
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Inflammasome and immune disorders
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
Izmir University
2015-2023
Dokuz Eylül University
2015-2022
La Jolla Institute for Immunology
2006-2018
University of Bonn
2005-2013
Zero to Three
2005
Institute of Molecular Medicine
2005
Invariant natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after activation, thereby impacting a wide variety different immune reactions. However, strong activation iNKT with α-galactosylceramide (αGalCer) reportedly induces hyporeactive state that resembles anergy. In contrast, we determined here from mice pretreated αGalCer retain cytotoxic activity and maintain the ability to respond TCR-dependent as well TCR-independent cytokine-mediated stimulation....
Abstract CpG‐rich oligonucleotides (CpG‐ODN) bind to Toll‐like receptor 9 (TLR9) and are used as powerful adjuvants for vaccination. Here we report that CpG‐ODN not only act immune stimulatory agents but can also induce strong suppression depending on the anatomical location of application. In agreement with adjuvant effect, subcutaneous application antigen plus resulted in antigen‐specific T cell activation local lymph nodes. contrast, systemic expansion CTL activity spleen. The suppressive...
Invariant NKT (iNKT) cells are a unique subset of T lymphocytes that rapidly carry out effector functions following activation with glycolipid Ags, such as the model Ag alpha-galactosylceramide. Numerous studies have investigated mechanisms leading to Th1 and Th2 cytokine production by iNKT cells, well effects copious amounts cytokines these produce. Less is known, however, about cell cytotoxicity. In this study, we effect availability strength, molecules involved in We demonstrate...
Abstract Commensal bacteria play an important role in formation of the immune system, but mechanisms involved are incompletely understood. In this study, we analyze CD1d-restricted invariant NKT (iNKT) cells germfree mice and two colonies C57BL/6 termed conventional flora restricted (RF), stably bearing commensal microbial communities diverse distinct composition. mice, iNKT were moderately reduced, suggesting that microbiota partially required for antigenic drive maintaining systemic cells....
Macrophages are highly plastic cells that can polarize into functionally distinct subsets in vivo and vitro response to environmental signals. The development of protocols model macrophage polarization greatly contributes our understanding biology. divided two main groups: Pro-inflammatory M1 macrophages (classically activated) anti-inflammatory M2 (alternatively activated), based on several key surface markers the production inflammatory mediators. However, expression these common is...
After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne induce tolerance. Here we investigated whether LSEC contribute to Oral were efficiently cross-presented on H-2K(b) by naive CD8 cells. Cross-presentation efficiency in but not dendritic was increased antigen-exposure heat or low pH. Mechanistically, cross-presentation requires...
Certain glycolipid Ags for Valpha14i NKT cells can direct the overall cytokine balance of immune response. Th2-biasing OCH has a lower TCR avidity than most potent agonist known, alpha-galactosylceramide. Although CD1d-exposed portions and alpha-galactosylceramide are identical, structural analysis indicates that there subtle CD1d conformational differences due to in buried lipid portion these two Ags, likely accounting difference antigenic potency. Th1-biasing C-glycoside/CD1d even weaker...
Invariant NKT cells (iNKT cells) are a unique subset of T lymphocytes that rapidly carry out effector functions. In this study, we report majority sterile house dust extracts (HDEs) tested contained antigens capable activating mouse and human iNKT cells. HDEs had adjuvant-like properties in an ovalbumin (OVA)-induced asthma model, which were dependent on Vα14i cells, as vaccinated animals deficient for displayed significantly attenuated immune responses airway inflammation. Furthermore, the...
Development of tumor-specific T cell tolerance contributes to the failure immune system eliminate tumor cells. Here we report that hematogenous dissemination cells followed by their elimination and local removal apoptotic in liver leads subsequent development towards antigens associated with We provide evidence sinusoidal endothelial (LSEC) remove fragments generated induction apoptosis through hepatic NK1.1+ Antigen material is processed cross-presented LSEC CD8+ cells, leading tolerance....
The present panel was optimized to quantify the relative frequency of majority major T cell subsets currently described within human peripheral blood mononuclear cells (PBMCs) via use surface markers (Table 1). This includes all CD4+ that received a helper—nomenclature date and Tregs. Furthermore, surrogate staining strategy for identification mNKT/MAIT without need Vα7.2 is proposed. has been validated fresh cryopreserved PBMCs. Other tissue types have not tested. Activated can...
Abstract Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including NKT (iNKT) cells and mucosal-associated (MAIT) cells. iNKT cell involvement in human asthma is controversial, whereas there has been little analysis MAIT Using peripheral blood from 110 participants the Urban Environment Childhood Asthma (URECA) birth cohort study, these were analyzed for number function. We determined whether or frequency at 1 y correlated...
Abstract Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based easier and cheaper produce do not require special storage/transportation conditions, they suitable for low-/middle-income countries. Here, we report our development studies with receptor binding domain of Delta Plus strain (RBD-DP) which caused increased hospitalizations compared other variants. First, expressed RBD-DP in Pichia pastoris yeast system upscaled it a...
Invariant NKT (iNKT) cells are a conserved αβTCR(+) T cell population that can swiftly produce large amounts of cytokines, thereby activating other leukocytes, including neutrophilic granulocytes (neutrophils). In this study, we investigated the reverse relationship, showing high neutrophil concentrations suppress iNKT response in mice and humans. Peripheral Vα14 from spontaneously produced reduced cytokines to model Ag α-galactosyl ceramide expressed lower T-box transcription factor 21...
Abstract In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with only change being single atom: substitution carbonyl oxygen sulfur atom. Although DB06-1 not more effective vitro, small has marked impact on ability lipid stimulate iNKT vivo, increased IFN-γ production at 24 h compared αGalCer,...
Invariant Natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after in vivo activation, allowing for the direct detection a number directly ex vivo. However, some this approach is suboptimal. Here, we report technical variations that allow improved IL-4, IL-10, IL-13 and IL-17A Furthermore, describe an alternative stimulation iNKT vitro allows significantly produced by cells. Together, these protocols cell with increased sensitivity.
Abstract Activation of invariant (i)NKT cells with the model Ag α-galactosylceramide induces rapid production multiple cytokines, impacting a wide variety different immune reactions. In contrast, following secondary activation α-galactosylceramide, behavior iNKT is altered for months, most cytokines being strongly reduced. The requirements induction this hyporesponsive state, however, remain poorly defined. study, we show that Th1-biasing cell Ags could induce hyporesponsiveness, as long...
ATP-binding cassette transporter G1 (ABCG1) plays a role in the intracellular transport of cholesterol. Invariant NKT (iNKT) cells are subpopulation T lymphocytes that recognize glycolipid Ags. In this study, we demonstrate ABCG1 regulates iNKT cell development and functions cell-intrinsic manner. Abcg1(-/-) mice displayed reduced frequencies thymus periphery. Thymic deficient had membrane lipid raft content, showed impaired proliferation defective maturation during early stages development....
Only recently have natural antigens for CD1d-dependent, invariant Valpha14+ killer T (iNKT) cells been identified. Similar data CD1d-independent and CD8+ NKT cell populations are still missing. Here, we show that the MHC class I-restricted TCR-transgenic mouse lines OT-I, P14 H-Y contain a significant proportion of transgenic NK1.1+ cells. In liver, most express CD8alphaalpha homodimers. Transgenic did not bind Valpha14-to-Jalpha18 TCR rearrangement (Valpha14i)-specific...