A5052181125- IL-33, ST2, and ILC Pathways
- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- Immune cells in cancer
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Heme Oxygenase-1 and Carbon Monoxide
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- Cannabis and Cannabinoid Research
- Cancer Cells and Metastasis
- Complement system in diseases
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Redox biology and oxidative stress
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Streptococcal Infections and Treatments
- Sphingolipid Metabolism and Signaling
- Whipple's Disease and Interleukins
- Renal Diseases and Glomerulopathies
- Eicosanoids and Hypertension Pharmacology
University of Geneva
2022-2025
Goethe University Frankfurt
2018-2024
Université de Limoges
2019
Inserm
2019
Contrôle de la Réponse Immune B et Lymphoproliférations
2017
Highlights•IL-38-deficient mice display delayed resolution of imiquimod-induced psoriasis•IL-38 suppresses IL-17A production by γδ T cells•Inhibition cells requires IL1RAPL1•IL1RAPL1-deficient show decreased cell activation during psoriasisSummaryInterleukin-38 (IL-38) is a cytokine the IL-1 family with role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 highly expressed skin downregulated psoriasis patients. We report an investigation...
We aimed at clarifying the role of lipocalin-2 (LCN-2) in clear-cell renal cell carcinoma (ccRCC). Since LCN-2 was recently identified as a novel iron transporter, we explored its load decisive factor conferring biological function.LCN-2 expression analysed mRNA and protein level by using immunohistochemistry, RNAscope® qRT-PCR patients diagnosed with compared adjacent healthy tissue. measured LCN-2-bound atomic absorption spectrometry from patient-derived samples applied functional assays...
The sphingolipid sphingosine-1-phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein-coupled receptors. cell-specific receptor 4 (S1pr4) was connected the generation of IL-17-producing T cells through regulation cytokine production innate cells. Therefore, we explored whether S1pr4 affected imiquimod-induced murine psoriasis IL-17 production. We did not observe altered production, although severity reduced S1pr4-deficient mice. Instead, ablation...
Interleukin (IL)-38 is an IL-1 family cytokine that was proposed to exert anti-inflammatory effects. However, its mechanisms of action are not well understood and the identity IL-38 receptor(s) remains debated. Proposed candidates include receptor (IL-1R1), IL-36 (IL-36R) orphan IL-1RAPL1. Yet, in literature, often presented as IL-36R antagonist. The N-terminus protein produced a human keratinocyte cell line endogenous epidermal isolated from healthy skin characterized by mass spectrometry....
Abstract Interleukin (IL)-18 is an immunoregulatory cytokine that acts as a potent inducer of T helper 1 and cytotoxic responses. IL-18 activity regulated by its decoy receptor binding protein (IL-18BP), which forms high-affinity complex with to block the cognate receptors. A disbalance between IL-18BP associated excessive signaling can lead systemic inflammation. Indeed, severity CpG-induced macrophage activation syndrome exacerbated in knockout (KO) mice. On contrary, targeting have...
Abstract IL-38 is an IL-1 family receptor antagonist that restricts IL-17–driven inflammation by limiting cytokine production from macrophages and T cells. In the current study, we aimed to explore its role in experimental autoimmune encephalomyelitis mice, which is, among others, driven IL-17. Unexpectedly, IL-38–deficient mice showed strongly reduced clinical scores histological markers of encephalomyelitis. This was accompanied inflammatory cell infiltrates, including cells, as well...
IL-38 is an IL-1 family receptor antagonist with emerging role in chronic inflammatory diseases. expression has been mainly observed not only epithelia, but also cells of the immune system, including macrophages and B cells. Given association both inflammation, we explored if affects cell biology. IL-38-deficient mice showed higher amounts plasma (PC) lymphoid organs but, conversely, lower levels plasmatic antibody titers. Exploring underlying mechanisms human revealed that exogenously added...
The lipid content of skin plays a determinant role in its barrier function with particularly important attributed to linoleic acid and derivatives. Here we explored the consequences interfering soluble epoxide hydrolase (sEH) on homeostasis. sEH; which converts fatty epoxides generated by cytochrome P450 enzymes their corresponding diols, was largely restricted epidermis enriched sEH-generated diols. Global deletion sEH increased levels epoxides, including acid-derived epoxide;...
Psoriasis is a common chronic inflammatory skin disease that significantly impacts the patients' quality of life. Recent studies highlighted function interleukin (IL)-1 family member IL-38 in homeostasis and suggested an anti-inflammatory role for this cytokine psoriasis. In study, we generated mice specifically overexpressing protein epidermal keratinocytes. We confirmed overexpression by Western blotting. further detected ELISA plasma, as well conditioned media explants isolated from mice,...
Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs). Computational analysis predicts LCRs in six the 11 members. Among these, IL-38 contains a long LCR including two amyloid cores. localizes intracellular keratinocytes under oxidative (OS) forms OS-induced aggregates...
Significance Statement IgA nephropathy (IgAN) is characterized by glomerular mesangial deposition, but its pathogenesis remains unclear. Using humanized transgenic mouse models, the authors explored whether a hypogalactosylated hinge region (found in most IgA1 human IgAN) required for demonstrating that hypoglycosylation was not mandatory deposition. To investigate low-affinity produced innate-like B cells might also yield deposits, they compared mice able to produce high-affinity mature...
Abstract Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E 2 (PGE ), are well-characterized mediators of inflammation. PGE is produced in an inducible manner macrophages (Mϕ) by microsomal -synthase-1 (mPGES-1), with notion that it also conveys pro-resolving properties. We aimed characterize role mPGES-1 during acute, zymosan-induced peritonitis. Experimentally, we applied inhibitor...
Inflammation plays a pivotal role in cancer development, with chronic inflammation promoting tumor progression and treatment resistance, whereas acute inflammatory responses contribute to protective anti-tumor immunity. Gasdermin D (GSDMD) mediates the release of pro-inflammatory cytokines such as IL-1β. While IL-1β is directly linked several types cancers, GSDMD less clear. In this study, we show that expression upregulated human breast, kidney, liver, prostate cancer. Higher correlated...
Murine acetaminophen-induced acute liver injury (ALI) serves as paradigmatic model for drug-induced hepatic and regeneration. As major cause of ALI, acetaminophen overdosing is a persistent therapeutic challenge with N-acetylcysteine clinically used to ameliorate parenchymal necrosis. To identify further treatment strategies that serve patients poor responses, 3'mRNA sequencing was performed in the initial resolution phase at 24 h/48 h after sublethal overdosing. This approach disclosed 45...
Despite the success of immune checkpoint blockade in cancer, number patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for blockade, which includes combining blocking agents such as anti-PD-1 antibodies with standard care treatments. Here we report a combination chemotherapy (doxorubicin) and (anti-PD-1 antibodies) induces superior tumor control compared alone murine autochthonous polyoma middle T...
The interaction of macrophages with apoptotic cells is required for efficient resolution inflammation. While cell removal prevents inflammation due to secondary necrosis, it also alters the macrophage phenotype hinder further inflammatory reactions. between and often studied by chemical or biological induction apoptosis, which may introduce artifacts affecting as well and/or triggering unrelated signaling pathways. Here, we set up a pure death system in NIH 3T3 expressing dimerizable...
Macrophages are a highly versatile and heterogenic group of immune cells, known for their involvement in inflammatory reactions. However, our knowledge about distinct subpopulations macrophages specific contribution to the resolution inflammation remains incomplete. We have previously shown, an vivo peritonitis model, that inhibition synthesis pro-inflammatory lipid mediator prostaglandin E2 (PGE2) attenuates efficient inflammation. PGE2 levels during later stages process further correlate...
Interleukin-38 (IL-38) is a cytokine of the IL-1 family with role in chronic inflammation. However, its main cellular targets and receptor(s) remain obscure. IL-38 highly expressed skin downregulated psoriasis patients. Therefore, we investigated during progression imiquimod-induced psoriasis. In this model, IL-38-knockout (IL-38 KO) mice showed delayed disease resolution due to exacerbated IL-17-mediated inflammation, which was reversed by administration mature IL-38. Mechanistically,...
Cytokines of the interleukin (IL)-1 family are widely expressed in epithelial surfaces, including epidermis, where they play a key role maintenance barrier integrity and host defense. A recent report associated IL-1 member IL-33 with stress granules (SGs) cells. Formation SGs is promoted by aggregation proteins harboring low complexity regions (LCRs). In this study, using computational analyses, we predicted presence LCRs six eleven members. Among these, IL-38 contained long LCR localized to...
Abstract Cytokines of the interleukin (IL)-1 family are widely expressed in epithelial surfaces, including epidermis, where they play a key role maintenance barrier integrity and host defense. A recent report associated IL-1 member IL-33 with stress granules (SGs) cells. Formation SGs is promoted by aggregation proteins harboring low complexity regions (LCRs). In this study, using computational analyses, we predicted presence LCRs six eleven members. Among these, IL-38 contained long LCR...