A5021240225- Adenosine and Purinergic Signaling
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Calcium signaling and nucleotide metabolism
- Extracellular vesicles in disease
- Neurological Complications and Syndromes
- Cytomegalovirus and herpesvirus research
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Ion Channels and Receptors
- Pneumocystis jirovecii pneumonia detection and treatment
- Galectins and Cancer Biology
- Kawasaki Disease and Coronary Complications
- Bioactive Compounds and Antitumor Agents
- Nanoplatforms for cancer theranostics
- Ion channel regulation and function
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Adolescent and Pediatric Healthcare
University Medical Center Hamburg-Eppendorf
2017-2025
Universität Hamburg
2017-2025
Eppendorf (Belgium)
2024
Abstract Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis extracellular ATP ectonucleotidases CD39 CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T contribute adenosine production releasing CD73-containing vesicles upon activation. These have AMPase activity, the resulting mediates suppression independently...
An increase in the extracellular concentration of ATP as a consequence cellular stress or cell death results activation immune cells. To prevent inflammation, is rapidly metabolized to adenosine, which deploys an anti-inflammatory signaling cascade upon binding P1 receptors on The ectonucleotidases necessary for degradation and generation adenosine are present membrane many cells, their expression tightly regulated under conditions inflammation. discovery that vesicles (EVs) carry purinergic...
Background An important mechanism, by which cancer cells achieve immune escape, is the release of extracellular adenosine into their microenvironment. Adenosine activates A 2A and 2B receptors on constituting one strongest immunosuppressive mediators. In addition, promotes angiogenesis, tumor cell proliferation, metastasis. Cancer upregulate ectonucleotidases, most importantly CD39 CD73, catalyze hydrolysis ATP to AMP (CD39) further (CD73). Inhibition thus expected be an effective strategy...
CD39 is the major enzyme controlling levels of extracellular adenosine triphosphate (ATP) via stepwise hydrolysis ATP to diphosphate (ADP) and monophosphate (AMP). As a strong promoter inflammation, monoclonal antibodies (mAbs) blocking are utilized therapeutically in field immune-oncology. Though anti-CD39 mAbs highly specific for their target, they lack deep penetration into dense tissue solid tumors, due large size. To overcome this limitation, we generated characterized nanobodies that...
Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39) catalyzes the extracellular hydrolysis of ATP generating AMP, while ecto-5'-nucleotidase (CD73) further hydrolyzes AMP yielding immunosuppressive adenosine. 8-Butylthioadenosine 5'-monophosphate (8-BuS-AMP) was described as a CD39 inhibitor but has been poorly characterized. The standard antagonist ARL 67156 is not suitable for in vivo studies due to metabolic instability. In present study, we optimized and upscaled synthesis...
Abstract Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro‐inflammatory cytokines in monocytes. However, a detailed analysis receptor expression function human T cell compartment has not been reported. Here, we used P2X7‐specific nanobody assess membrane on peripheral lymphocyte subsets. The results show that innate‐like cells, which effectively react innate stimuli by secreting high amounts cytokines, have highest compartment. Using Tγδ...
T cell activation starts with formation of second messengers that release Ca2+ from the endoplasmic reticulum (ER) and thereby activate store-operated entry (SOCE), one essential signals for activation. Recently, steroidal 2-methoxyestradiol was shown to inhibit nuclear translocation factor activated cells (NFAT). We therefore investigated inhibition in cells, screened a library analogues, characterized derivative 2-ethyl-3-sulfamoyloxy-17β-cyanomethylestra-1,3,5(10)-triene (STX564) as...
Mouse T cells express the ecto-ADP-ribosyltransferase ARTC2.2, which can transfer ADP-ribose group of extracellular nicotinamide adenine dinucleotide (NAD + ) to arginine residues various cell surface proteins thereby influencing their function. Several targets such as P2X7, CD8a and CD25 have been identified, however a comprehensive mouse ADP-ribosylome analysis is currently missing. Using Af1521 macrodomain-based enrichment ADP-ribosylated peptides mass spectrometry, we identified 93...
Local, sub-second Ca