A5088361290- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Inflammasome and immune disorders
- Complement system in diseases
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Dermatology and Skin Diseases
- Vibrio bacteria research studies
- Neurobiology and Insect Physiology Research
- Blood groups and transfusion
- Viral Infectious Diseases and Gene Expression in Insects
- IL-33, ST2, and ILC Pathways
- Diabetes and associated disorders
- Invertebrate Immune Response Mechanisms
- Urticaria and Related Conditions
- Vitamin C and Antioxidants Research
- Whipple's Disease and Interleukins
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
The Francis Crick Institute
2018-2023
Trinity College Dublin
2012-2020
Science Foundation Ireland
2011
Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to other members family, IL-36 are expressed inactive precursors require proteolytic processing for activation; however, responsible proteases unknown. Here, we show that activated differentially by neutrophil granule-derived cathepsin G, elastase, proteinase-3, increasing their biological activity ∼500-fold. Active promoted a strong pro-inflammatory...
Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil play an important role in coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines initiators inflammation typically released via necrosis require proteolytic processing for activation. Here, we...
Activated neutrophils can undergo a mode of regulated cell death, called NET osis, that results in the extrusion chromatin into extracellular space, thereby acting as traps for microorganisms. Neutrophil‐derived ( s) are comprised DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such elastase cathepsin G (Cat G). ‐associated factors thought to enhance properties these structures localisation molecules on s may serve increase their local concentration....
Abstract Sterile inflammation is initiated by molecules released from necrotic cells, called damage-associated molecular patterns (DAMPs). Members of the extended IL-1 cytokine family are important DAMPs, typically only through necrosis, and require limited proteolytic processing for activation. The cytokines, IL-36α, IL-36β, IL-36γ, expressed as inactive precursors have been implicated key initiators psoriatic-type skin inflammation. We recently found that IL-36 cytokines proteolytically...
Damage-associated molecular patterns (DAMPs) are molecules exposed or released by dead cells that trigger modulate immunity and tissue repair. In vertebrates, the cytoskeletal component F-actin is a DAMP specifically recognised DNGR-1, an innate immune receptor. Previously we suggested actin also in
IL‐1 family cytokines act as apical initiators of inflammation in many settings and can promote the production a battery inflammatory cytokines, chemokines other mediators diverse cell types. IL‐36α, IL‐36β IL‐36γ, which belong to extended family, have been implicated key skin psoriasis. IL‐36γ is highly upregulated lesional from psoriatic individuals, heritable mutations natural IL‐36 receptor antagonist result severe form are initially expressed inactive precursors that require proteolytic...
Recent evidence has strongly implicated IL‐36 cytokines as key initiators of inflammation in the skin barrier. belong to extended IL‐1 family and, similar most members this family, are expressed inactive precursors that require proteolytic processing for activation. Because proteases responsible activation subfamily have not been reported, we developed a method production biologically active through introduction caspase cleavage motif, DEVD, within N‐termini these cytokines. Here, show...
Cross-presentation of dead cell-associated antigens by conventional dendritic cells type 1 (cDC1s) is critical for CD8+ T response against many tumors and viral infections. It facilitated DNGR-1 (CLEC9A), an SYK-coupled cDC1 receptor that detects cell debris. Here, we report engagement leads to rapid activation CBL CBL-B E3 ligases cause K63-linked ubiquitination SYK terminate signaling. Genetic deletion or charge-conserved mutation target lysines within abolishes results in enhanced...