Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 ...
Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 ...
Glucocorticoids (GCs) have been used clinically for decades as potent anti-inflammatory and immunosuppressive agents. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of glucocorticoid resistance (GCR). Therefore, efforts to understand the complex mechanisms underlying GC function and GCR are on...
The CARD-coiled coil (CC)/Bcl10/MALT1-like paracaspase (CBM) signaling complexes composed of a CARD-CC family member (CARD-9, -10, -11, or -14), Bcl10, and the type 1 paracaspase MALT1 (PCASP1) play a pivotal role in immunity, inflammation, and cancer. Targeting MALT1 proteolytic activity is of potential therapeutic interest. However, little is kno...
A20 is a negative regulator of NF-kappa B signaling; it controls inflammatory responses and ensures tissue homeostasis. A20 is thought to restrict NF-kappa B activation both by its ubiquitin-editing activity as well as by its nonenzymatic activities. Besides its role in NF-kappa B signaling, A20 also acts as a protective factor inhibiting apoptosis...
Sepsis, a systemic inflammation as a response to a bacterial infection, is a huge unmet medical need. Data accumulated over the last decade suggest that the nutritional status of patients as well as composition of their gut microbiome, are strongly linked with the risk to develop sepsis, the severity of the disease and prognosis. In particular, the...
Background: It is currently unknown why allergen exposure or environmental triggers in patients with mild-to-moderate asthma result in T(H)2-mediated eosinophilic inflammation, whereas patients with severe asthma often present with T(H)17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both T(H)2 and...
Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor kappa B (NF-kappa B)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation can directly repress TNF-induced death. Here, we show that ubiquitylation regulates RI...
Optineurin (OPTN) was identified 20 years ago in a yeast-two-hybrid screen with a viral protein known to inhibit the cytolytic effects of tumor necrosis factor. Since then, OPTN has been identified as a ubiquitin-binding protein involved in many signaling pathways and cellular processes, and mutations in the OPTN gene have been associated with glau...
