19 results on '"Bonefeld, Charlotte Menne"'
Search Results
2. An overview of tolerance creation in thymus - An updated model based on newer research
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Bonefeld, Charlotte Menne, Esbensen, Anders Fromm, Bonefeld, Charlotte Menne, and Esbensen, Anders Fromm
- Abstract
Tolerance is an essential part of the process of creating functional immune cells. A dysfunctional tolerance will usually lead to autoreactive immune cells that causes autoimmune diseases. As a lot of new research on tolerance comes out, it can be hard to get a full overview of what the newest research tells us. The objective of this paper was to create a better overview of the process of tolerance creation. It reviews relevant research and literature, to explain our current model for tolerance and show how newer research can be used to create a more comprehensive model.
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- 2022
3. Low SATB1 Expression Promotes IL-5 and IL-9 Expression in Sézary Syndrome
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Herrera, Alberto, Fredholm, Simon, Cheng, Anthony, Mimitou, Eleni P., Seffens, Angelina, Bar-Natan, Michal, Sun, Amy, Latkowski, Jo-Ann, Willerslew-Olsen, Andreas, Buus, Terkild B., Gluud, Maria, Krejsgaard, Thorbjørn, Torres-Rusillo, Sara, Bonefeld, Charlotte Menné, Woetmann, Anders, Geisler, Carsten, Geskin, Larisa J., Ouyang, Zhengqing, Smibert, Peter, Ødum, Niels, and Koralov, Sergei B.
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- 2020
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4. MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
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Gluud, Maria, Willerslev-Olsen, Andreas, Gjerdrum, Lise Mette Rahbek, Lindahl, Lise M., Buus, Terkild B., Andersen, Mads Hald, Bonefeld, Charlotte Menne, Krejsgaard, Thorbjorn, Litvinov, Ivan V., Iversen, Lars, Becker, Jürgen C., Persson, Jenny L., Koralov, Sergei B., Litman, Thomas, Geisler, Carsten, Woetmann, Anders, Odum, Niels, Gluud, Maria, Willerslev-Olsen, Andreas, Gjerdrum, Lise Mette Rahbek, Lindahl, Lise M., Buus, Terkild B., Andersen, Mads Hald, Bonefeld, Charlotte Menne, Krejsgaard, Thorbjorn, Litvinov, Ivan V., Iversen, Lars, Becker, Jürgen C., Persson, Jenny L., Koralov, Sergei B., Litman, Thomas, Geisler, Carsten, Woetmann, Anders, and Odum, Niels
- Abstract
Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
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- 2020
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5. MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
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Gluud, Maria, primary, Willerslev-Olsen, Andreas, additional, Gjerdrum, Lise Mette Rahbek, additional, Lindahl, Lise M., additional, Buus, Terkild B., additional, Andersen, Mads Hald, additional, Bonefeld, Charlotte Menne, additional, Krejsgaard, Thorbjorn, additional, Litvinov, Ivan V., additional, Iversen, Lars, additional, Becker, Jürgen C., additional, Persson, Jenny L., additional, Koralov, Sergei B., additional, Litman, Thomas, additional, Geisler, Carsten, additional, Woetmann, Anders, additional, and Odum, Niels, additional
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- 2020
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6. Inflammation induced PD-L1-specific T cells
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Munir, Shamaila, Lundsager, Mia Thorup, Jørgensen, Mia Aabroe, Hansen, Morten, Petersen, Trine Hilkjær, Bonefeld, Charlotte Menne, Friese, Christina, Met, Özcan, Straten, Per Thor, Andersen, Mads Hald, Munir, Shamaila, Lundsager, Mia Thorup, Jørgensen, Mia Aabroe, Hansen, Morten, Petersen, Trine Hilkjær, Bonefeld, Charlotte Menne, Friese, Christina, Met, Özcan, Straten, Per Thor, and Andersen, Mads Hald
- Abstract
PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.
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- 2019
7. Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
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Blumel, Edda, Willerslev-Olsen, Andreas, Gluud, Maria, Lindahl, Lise M., Fredholm, Simon, Nastasi, Claudia, Krejsgaard, Thorbjorn, Surewaard, Bas G. J., Koralov, Sergei B., Hu, Tengpeng, Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Iversen, Lars, Becker, Juergen C., Andersen, Mads Hald, Woetmann, Anders, Buus, Terkild Brink, Odum, Niels, Blumel, Edda, Willerslev-Olsen, Andreas, Gluud, Maria, Lindahl, Lise M., Fredholm, Simon, Nastasi, Claudia, Krejsgaard, Thorbjorn, Surewaard, Bas G. J., Koralov, Sergei B., Hu, Tengpeng, Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Iversen, Lars, Becker, Juergen C., Andersen, Mads Hald, Woetmann, Anders, Buus, Terkild Brink, and Odum, Niels
- Abstract
Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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- 2019
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8. Inflammation induced PD-L1-specific T cells
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Munir, Shamaila, primary, Lundsager, Mia Thorup, additional, Jørgensen, Mia Aabroe, additional, Hansen, Morten, additional, Petersen, Trine Hilkjær, additional, Bonefeld, Charlotte Menne, additional, Friese, Christina, additional, Met, Özcan, additional, Straten, Per thor, additional, and Andersen, Mads Hald, additional
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- 2019
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9. Single-cell heterogeneity in Sézary syndrome
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Buus, Terkild Brink, Willerslev-Olsen, Andreas, Fredholm, Simon, Blumel, Edda, Nastasi, Claudia, Gluud, Maria, Hu, Tengpeng, Lindahl, Lise M., Iversen, Lars, Fogh, Hanne, Gniadecki, Robert, Litvinov, Ivan V., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Christensen, Jan Praysgaard, Krejsgaard, Thorbjorn, Litman, Thomas, Woetmann, Anders, Odum, Niels, Buus, Terkild Brink, Willerslev-Olsen, Andreas, Fredholm, Simon, Blumel, Edda, Nastasi, Claudia, Gluud, Maria, Hu, Tengpeng, Lindahl, Lise M., Iversen, Lars, Fogh, Hanne, Gniadecki, Robert, Litvinov, Ivan V., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Christensen, Jan Praysgaard, Krejsgaard, Thorbjorn, Litman, Thomas, Woetmann, Anders, and Odum, Niels
- Abstract
Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
- Published
- 2018
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10. SATB1 in malignant T cells
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Fredholm, Simon Mayland, Willerslev-Olsen, Andreas, Met, Özcan, Kubat, Linda, Gluud, Maria, Mathiasen, Sarah L., Friese, Christina, Blümel, Edda, Petersen, David Leander, Hu, Tengpeng, Nastasi, Claudia, Lindahl, Lise M., Buus, Terkild Brink, Krejsgaard, Thorbjørn Frej, Wasik, Mariusz A., Kopp, Katharina Luise Maria, Koralov, Sergei B., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Andersen, Anders Woetmann, Iversen, Lars, Becker, Jürgen C., Ødum, Niels, Fredholm, Simon Mayland, Willerslev-Olsen, Andreas, Met, Özcan, Kubat, Linda, Gluud, Maria, Mathiasen, Sarah L., Friese, Christina, Blümel, Edda, Petersen, David Leander, Hu, Tengpeng, Nastasi, Claudia, Lindahl, Lise M., Buus, Terkild Brink, Krejsgaard, Thorbjørn Frej, Wasik, Mariusz A., Kopp, Katharina Luise Maria, Koralov, Sergei B., Persson, Jenny L., Bonefeld, Charlotte Menne, Geisler, Carsten, Andersen, Anders Woetmann, Iversen, Lars, Becker, Jürgen C., and Ødum, Niels
- Abstract
Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic Jak3/STAT5/miR-155 pathway, SATB1, and cytokines linked to CTCL severity and progression indicating that SATB1 dysregulation is involved in CTCL pathogenesis.
- Published
- 2018
11. Nickel acts as an adjuvant during cobalt sensitization
- Author
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Bonefeld, Charlotte Menne, Nielsen, Morten Milek, Vennegaard, Marie T., Johansen, Jeanne Duus, Geisler, Carsten, Thyssen, Jacob Pontoppidan, Bonefeld, Charlotte Menne, Nielsen, Morten Milek, Vennegaard, Marie T., Johansen, Jeanne Duus, Geisler, Carsten, and Thyssen, Jacob Pontoppidan
- Published
- 2015
12. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation
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Krejsgaard, Thorbjørn Frej, Willerslev-Olsen, Andreas, Lindahl, Lise Maria, Bonefeld, Charlotte Menne, Koralov, Sergei B., Geisler, Carsten, Wasik, Mariusz A., Gniadecki, Robert, Kilian, Mogens, Iversen, Lars, Andersen, Anders Woetmann, Ødum, Niels, Krejsgaard, Thorbjørn Frej, Willerslev-Olsen, Andreas, Lindahl, Lise Maria, Bonefeld, Charlotte Menne, Koralov, Sergei B., Geisler, Carsten, Wasik, Mariusz A., Gniadecki, Robert, Kilian, Mogens, Iversen, Lars, Andersen, Anders Woetmann, and Ødum, Niels
- Abstract
Patients with cutaneous T-cell lymphoma (CTCL) are frequently colonized with Staphylococcus aureus (SA). Eradication of SA is, importantly, associated with significant clinical improvement suggesting that SA promotes the disease activity but the underlying mechanisms remain poorly characterized. Here we show that SA isolates from involved skin express staphylococcal enterotoxins (SEs) which induce cross-talk between malignant and benign T cells leading to Stat3-mediated IL-10 production by the malignant T cells. The SEs did not stimulate the malignant T cells directly. Instead, SEs triggered a cascade of events involving cell-cell and asymmetric cytokine interactions between malignant and benign T cells, which stimulated the malignant T cells to express high levels of IL-10. Much evidence supports that malignant activation of the Stat3/IL-10 axis plays a key role in driving the immune dysregulation and severe immunodeficiency that characteristically develops in CTCL patients. The present findings thereby establish a novel link between SEs and immune dysregulation in CTCL strengthening the rationale for antibiotic treatment of colonized patients with severe or progressive disease.
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- 2014
13. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma
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Willerslev-Olsen, Andreas, Krejsgaard, Thorbjørn, Lindahl, Lise Maria, Bonefeld, Charlotte Menne, Wasik, Mariusz A, Koralov, Sergei B, Geisler, Carsten, Kilian, Mogens, Iversen, Lars, Woetmann, Anders, Odum, Niels, Willerslev-Olsen, Andreas, Krejsgaard, Thorbjørn, Lindahl, Lise Maria, Bonefeld, Charlotte Menne, Wasik, Mariusz A, Koralov, Sergei B, Geisler, Carsten, Kilian, Mogens, Iversen, Lars, Woetmann, Anders, and Odum, Niels
- Abstract
In patients with cutaneous T-cell lymphoma (CTCL) bacterial infections constitute a major clinical problem caused by compromised skin barrier and a progressive immunodeficiency. Indeed, the majority of patients with advanced disease die from infections with bacteria, e.g., Staphylococcus aureus. Bacterial toxins such as staphylococcal enterotoxins (SE) have long been suspected to be involved in the pathogenesis in CTCL. Here, we review links between bacterial infections and CTCL with focus on earlier studies addressing a direct role of SE on malignant T cells and recent data indicating novel indirect mechanisms involving SE- and cytokine-driven cross-talk between malignant- and non-malignant T cells.
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- 2013
14. Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway
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Krejsgaard, Thorbjørn Frej, Ralfkiær, Ulrik, Clasen-Linde, Erik, Eriksen, Karsten Wessel Kam, Kopp, Katharina Luise Maria, Bonefeld, Charlotte Menne, Geisler, Carsten, Dabelsteen, Sally, Wasik, Mariusz A., Ralfkiaer, Elisabeth Methner, Andersen, Anders Woetmann, Ødum, Niels, Krejsgaard, Thorbjørn Frej, Ralfkiær, Ulrik, Clasen-Linde, Erik, Eriksen, Karsten Wessel Kam, Kopp, Katharina Luise Maria, Bonefeld, Charlotte Menne, Geisler, Carsten, Dabelsteen, Sally, Wasik, Mariusz A., Ralfkiaer, Elisabeth Methner, Andersen, Anders Woetmann, and Ødum, Niels
- Abstract
IL-17 is a proinflammatory cytokine that is crucial for the host's protection against a range of extracellular pathogens. However, inappropriately regulated expression of IL-17 is associated with the development of inflammatory diseases and cancer. In cutaneous T-cell lymphoma (CTCL), malignant T cells gradually accumulate in skin lesions characterized by massive chronic inflammation, suggesting that IL-17 could be involved in the pathogenesis. In this study we show that IL-17 protein is present in 10 of 13 examined skin lesions but not in sera from 28 CTCL patients. Importantly, IL-17 expression is primarily observed in atypical lymphocytes with characteristic neoplastic cell morphology. In accordance, malignant T-cell lines from CTCL patients produce IL-17 and the synthesis is selectively increased by IL-2 receptor ß chain cytokines. Small-molecule inhibitors or small interfering RNA against Jak3 and signal transducer and activator of transcription 3 (Stat3) reduce the production of IL-17, showing that the Jak3/Stat3 pathway promotes the expression of the cytokine. In summary, our findings indicate that the malignant T cells in CTCL lesions express IL-17 and that this expression is promoted by the Jak3/Stat3 pathway.
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- 2011
15. TCR down-regulation boosts T-cell-mediated cytotoxicity and protection against poxvirus infections
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Hansen, Ann Kathrine, Regner, Matthias, Bonefeld, Charlotte Menne, Boding, Lasse, Kongsbak-Wismann, Martin, Ødum, Niels, Müllbacher, Arno, Geisler, Carsten, von Essen, Marina Rode, Hansen, Ann Kathrine, Regner, Matthias, Bonefeld, Charlotte Menne, Boding, Lasse, Kongsbak-Wismann, Martin, Ødum, Niels, Müllbacher, Arno, Geisler, Carsten, and von Essen, Marina Rode
- Abstract
Cytotoxic T (Tc) cells play a key role in the defense against virus infections. Tc cells recognize infected cells via the T-cell receptor (TCR) and subsequently kill the target cells by one or more cytotoxic mechanisms. Induction of the cytotoxic mechanisms is finely tuned by the activation signals from the TCR. To determine whether TCR down-regulation affects the cytotoxicity of Tc cells, we studied TCR down-regulation-deficient CD3¿LLAA mice. We found that Tc cells from CD3¿LLAA mice have reduced cytotoxicity due to a specific deficiency in exocytosis of lytic granules. To determine whether this defect was reflected in an increased susceptibility to virus infections, we studied the course of ectromelia virus (ECTV) infection. We found that the susceptibility to ECTV infection was significantly increased in CD3¿LLAA mice with a mortality rate almost as high as in granzyme B knock-out mice. Finally, we found that TCR signaling in CD3¿LLAA Tc cells caused highly increased tyrosine phosphorylation and activation of the c-Cbl ubiquitin ligase, and that the impaired exocytosis of lytic granules could be rescued by the knockdown of c-Cbl. Thus, our work demonstrates that TCR down-regulation critically increases Tc cell cytotoxicity and protection against poxvirus infection.
- Published
- 2011
16. Consumer available permanent hair dye products cause major allergic immune activation in an animal model
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Bonefeld, Charlotte Menne, Larsen, Jeppe Madura, Dabelsteen, Sally, Geisler, Carsten, White, I. R., Menne, Torkil, Johansen, Jeanne Duus, Bonefeld, Charlotte Menne, Larsen, Jeppe Madura, Dabelsteen, Sally, Geisler, Carsten, White, I. R., Menne, Torkil, and Johansen, Jeanne Duus
- Abstract
Udgivelsesdato: 2009-Jul-20, Summary Background p-Phenylenediamine (PPD) and related substances are ingredients of more than two-thirds of oxidative (permanent) hair dyes currently used. Although PPD is a potent skin sensitizer in predictive assays, the extent to which permanent hair dyes sensitize humans has been questioned due to the in-use conditions, e.g. the presence of couplers in the hair dye gel and rapid oxidation using a developer. Objectives To study the skin sensitizing potential of permanent hair dyes in mice. Methods Two different permanent hair dye products containing PPD were studied in CBA mice using a modified version of the local lymph node assay. The colour gel and developer (oxidant) were tested separately and in combination. Response was measured by ear swelling and cytokine production in ear tissue and serum by enzyme-linked immunosorbent assay. The immune cellular response in the draining lymph nodes was analysed by flow cytometry. Results Application of the colour gel both alone and mixed with the developer induced skin production of interleukin (IL)-1beta, tumour necrosis factor-alpha and IL-6 as well as systemic IL-6 release. Both treatments induced B- and T-cell infiltration as well as T-cell proliferation within the draining lymph nodes. Treatment with the mixture induced at least 20% more skin inflammation, cytokine production and CD4+ T-cell activation compared with the colour gel alone. Conclusions Consumer available PPD-containing permanent hair dyes can be potent and rapid immune activators. Mixing the colour gel and developer (oxidant) increased the induction of skin inflammation compared with application of the colour gel alone.
- Published
- 2010
17. Bonefeld, Charlotte Menne
- Author
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Bonefeld, Charlotte Menne and Bonefeld, Charlotte Menne
- Published
- 2006
18. Malignant T cells induce skin barrier defects through cytokine-mediated JAK/STAT signaling in cutaneous T-cell lymphoma
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Gluud, Maria, Pallesen, Emil M.H., Buus, Terkild B., Gjerdrum, Lise Mette Rahbek, Lindahl, Lise M., Kamstrup, Maria R., Bzorek, Michael, Danielsen, Maria, Bech, Rikke, Monteiro, Madalena N., Blümel, Edda, Willerslev-Olsen, Andreas, Lykkebo-Valløe, Anders, Vadivel, Chella Krishna, Krejsgaard, Thorbjørn, Bonefeld, Charlotte Menne, Geisler, Carsten, Becker, Jürgen C., Koralov, Sergei B., Iversen, Lars, Litman, Thomas, Woetmann, Anders, and Ødum, Niels
- Abstract
Cutaneous T-cell lymphoma (CTCL) is a devastating lymphoid malignancy characterized by the accumulation of malignant T cells in the dermis and epidermis. Skin lesions cause serious symptoms that hamper quality of life and are entry sites for bacterial infection, a major cause of morbidity and mortality in advanced diseases. The mechanism driving the pathological processes that compromise the skin barrier remains unknown. Here, we report increased transepidermal water loss and compromised expression of the skin barrier proteins filaggrin and filaggrin-2 in areas adjacent to TOX-positive T cells in CTCL skin lesions. Malignant T cells secrete mediators (including cytokines such as interleukin 13 [IL-13], IL-22, and oncostatin M) that activate STAT3 signaling and downregulate filaggrin and filaggrin-2 expression in human keratinocytes and reconstructed human epithelium. Consequently, the repression of filaggrins can be counteracted by a cocktail of antibodies targeting these cytokines/receptors, small interfering RNA–mediated knockdown of JAK1/STAT3, and JAK1 inhibitors. Notably, we show that treatment with a clinically approved JAK inhibitor, tofacitinib, increases filaggrin expression in lesional skin from patients with mycosis fungoides. Taken together, these findings indicate that malignant T cells secrete cytokines that induce skin barrier defects via a JAK1/STAT3-dependent mechanism. As clinical grade JAK inhibitors largely abrogate the negative effect of malignant T cells on skin barrier proteins, our findings suggest that such inhibitors provide novel treatment options for patients with CTCL with advanced disease and a compromised skin barrier.
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- 2022
- Full Text
- View/download PDF
19. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma.
- Author
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Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Bonefeld CM, Wasik MA, Koralov SB, Geisler C, Kilian M, Iversen L, Woetmann A, and Odum N
- Subjects
- Bacterial Infections complications, Cytokines, Disease Progression, Drug Resistance, Bacterial, Enterotoxins toxicity, Genes, T-Cell Receptor beta, Humans, Lymphoma, T-Cell, Cutaneous drug therapy, Lymphoma, T-Cell, Cutaneous pathology, Morbidity, Prevalence, Skin Neoplasms drug therapy, Skin Neoplasms microbiology, Skin Neoplasms pathology, Staphylococcus aureus metabolism, T-Lymphocytes pathology, Bacterial Infections pathology, Bacterial Toxins toxicity, Lymphoma, T-Cell, Cutaneous microbiology
- Abstract
In patients with cutaneous T-cell lymphoma (CTCL) bacterial infections constitute a major clinical problem caused by compromised skin barrier and a progressive immunodeficiency. Indeed, the majority of patients with advanced disease die from infections with bacteria, e.g., Staphylococcus aureus. Bacterial toxins such as staphylococcal enterotoxins (SE) have long been suspected to be involved in the pathogenesis in CTCL. Here, we review links between bacterial infections and CTCL with focus on earlier studies addressing a direct role of SE on malignant T cells and recent data indicating novel indirect mechanisms involving SE- and cytokine-driven cross-talk between malignant- and non-malignant T cells.
- Published
- 2013
- Full Text
- View/download PDF
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