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152. The effect of short-chain fatty acids on human monocyte-derived dendritic cells

Author

Nastasi, Claudia, primary, Candela, Marco, additional, Bonefeld, Charlotte Menné, additional, Geisler, Carsten, additional, Hansen, Morten, additional, Krejsgaard, Thorbjørn, additional, Biagi, Elena, additional, Andersen, Mads Hald, additional, Brigidi, Patrizia, additional, Ødum, Niels, additional, Litman, Thomas, additional, and Woetmann, Anders, additional

Published
2015
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154. Mechanisms behind Functional Avidity Maturation in T Cells

Author

von Essen, Marina Rode, Kongsbak, Martin, and Geisler, Carsten

Subjects
Article Subject, chemical and pharmacologic phenomena
Abstract

During an immune response antigen-primed B-cells increase their antigen responsiveness by affinity maturation mediated by somatic hypermutation of the genes encoding the antigen-specific B-cell receptor (BCR) and by selection of higher-affinity B cell clones. Unlike the BCR, the T-cell receptor (TCR) cannot undergo affinity maturation. Nevertheless, antigen-primed T cells significantly increase their antigen responsiveness compared to antigen-inexperienced (naïve) T cells in a process called functional avidity maturation. This paper covers studies that describe differences in T-cell antigen responsiveness during T-cell differentiation along with examples of the mechanisms behind functional avidity maturation in T cells.

Published
2012
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155. Endolysin Inhibits Skin Colonization by Patient-Derived Staphylococcus Aureusand Malignant T-Cell Activation in Cutaneous T-Cell Lymphoma

Author

Pallesen, Emil M.H., Gluud, Maria, Vadivel, Chella Krishna, Buus, Terkild B., de Rooij, Bob, Zeng, Ziao, Ahmad, Sana, Willerslev-Olsen, Andreas, Röhrig, Christian, Kamstrup, Maria R., Bay, Lene, Lindahl, Lise, Krejsgaard, Thorbjørn, Geisler, Carsten, Bonefeld, Charlotte M., Iversen, Lars, Woetmann, Anders, Koralov, Sergei B., Bjarnsholt, Thomas, Frieling, Johan, Schmelcher, Mathias, and Ødum, Niels

Abstract

Staphylococcus aureusis suspected to fuel disease activity in cutaneous T-cell lymphomas. In this study, we investigate the effect of a recombinant, antibacterial protein, endolysin (XZ.700), on S. aureusskin colonization and malignant T-cell activation. We show that endolysin strongly inhibits the proliferation of S. aureusisolated from cutaneous T-cell lymphoma skin and significantly decreases S. aureusbacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S. aureusis profoundly inhibited by endolysin. Moreover, endolysin inhibits the patient-derived S. aureusinduction of IFNγand the IFNγ-inducible chemokine CXCL10in healthy skin. Whereas patient-derived S. aureusstimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving nonmalignant T cells, endolysin strongly inhibits the effects of S. aureuson activation (reduced CD25 and signal transducer and activator of transcription 5 phosphorylation) and proliferation (reduced Ki-67) of malignant T cells and cell lines in the presence of nonmalignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureusand blocks their potential tumor-promoting effects on malignant T cells.

Published
2023
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159. Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

Author

Lauenborg, Britt, primary, Christensen, Louise, additional, Ralfkiaer, Ulrik, additional, Kopp, Katharina L., additional, Jønson, Lars, additional, Dabelsteen, Sally, additional, Bonefeld, Charlotte M., additional, Geisler, Carsten, additional, Gjerdrum, Lise Mette R., additional, Zhang, Qian, additional, Wasik, Mariusz A., additional, Ralfkiaer, Elisabeth, additional, Ødum, Niels, additional, and Woetmann, Anders, additional

Published
2015
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160. Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

Author

Bagdonaite, Ieva, primary, Wandall, Hans H., additional, Litvinov, Ivan V., additional, Nastasi, Claudia, additional, Becker, Jürgen C., additional, Dabelsteen, Sally, additional, Geisler, Carsten, additional, Bonefeld, Charlotte M., additional, Zhang, Qian, additional, Wasik, Mariusz A., additional, Zhou, Youwen, additional, Sasseville, Denis, additional, Ødum, Niels, additional, and Woetmann, Anders, additional

Published
2015
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164. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells.

Author

Schmidt, Jonas D., Ahlström, Malin G., Johansen, Jeanne D., Dyring ‐ Andersen, Beatrice, Agerbeck, Christina, Nielsen, Morten M., Poulsen, Steen S., Woetmann, Anders, Ødum, Niels, Thomsen, Allan R., Geisler, Carsten, and Bonefeld, Charlotte M.

Subjects
INTERLEUKIN-17, INTERFERONS, REGULATION of secretion, SECRETION, CD8 antigen, PHYSIOLOGY
Abstract

Background Skin-resident memory T (TRM) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore, the mechanisms whereby TRM cells induce rapid recall responses need further investigation. Objectives To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. Methods To address these questions, we analysed responses to contact allergens in mice and humans sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. Results Challenge responses in both mice and humans were dramatically increased at sites previously exposed to allergens as compared with previously unexposed sites. Importantly, the magnitude of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)-γ-producing TRM cells. Moreover, IL-17A and IFN-γ enhanced allergen-induced IL-1β production in keratinocytes. Conclusions We show that sensitization with contact allergens induces a strong, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8+ TRM cells. [ABSTRACT FROM AUTHOR]

Published
2017
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165. Detection of local inflammation induced by repeated exposure to contact allergens by use of IVIS Spectrum CT analyses.

Author

Nielsen, Morten M., Schmidt, Jonas D., Christensen, Jan P., Geisler, Carsten, Johansen, Jeanne D., and Bonefeld, Charlotte M.

Subjects
SKIN inflammation diagnosis, SKIN disease diagnosis, ALLERGENS, IMMUNOREGULATION, PHENOTYPES, THERAPEUTICS
Abstract

Background Contact allergy is characterized by local skin inflammation that, in some cases, can result in systemic immune activation. Objectives To investigate whether IVIS SpectrumCT analyses can be used to detect the immune response induced by contact allergens. Methods Mice were repeatedly exposed to vehicle or allergens on the ears. The local and systemic responses were analysed at different times with the ProSense 750 FAST probe in IVIS SpectrumCT measurements. In addition, changes in ear thickness, cytokine profile in the skin and immunological phenotype in the draining lymph nodes and spleen were determined. Results Local inflammation was detected by ProSense 750 FAST and correlated with changes in ear thickness, cytokine profile and immunological phenotype following exposure to the strong contact allergen 2,4-dinitrofluorobenzene. Analysis of the systemic response with ProSense 750 FAST did not show any difference between allergen-exposed and control mice, although fluorescence-activated cell sorting analysis of the spleen showed increased numbers of γδ T cells and CD11b+ CD11c+ MHCII+ cells in allergen-treated mice. Conclusions IVIS SpectrumCT analyses with ProSense 750 FAST as the probe can be used to detect local immune responses induced by contact allergens. [ABSTRACT FROM AUTHOR]

Published
2017
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166. The major diversification of Vγ1.1+ and Vγ2+ thymocytes in mice occurs after commitment to the γδ T-cell lineage.

Author

Buus, Terkild B., Geisler, Carsten, and Lauritsen, Jens Peter H.

Abstract

γδ T cells are a heterogeneous cell population with different subsets playing specialized and often opposing roles during immune responses. A key question is whether γδ thymocytes are determined for their effector function already at an early stage, before their commitment to the γδ T-cell lineage, or are instructed during their later development. Here, we show that the adult Vγ1.1+ and Vγ2+ γδ T-cell subsets both go through a CD73+CD24+ development stage, and that the gene regulation involved in lineage commitment is shared by both subsets. We demonstrate that the major subset diversification first occurs after the cells have committed to the γδ T-cell lineage, strongly supporting an instructive model for functional programming of γδ T cells. In conclusion, we show that the two major adult γδ T-cell subsets in mice develop through a shared pathway utilizing similar cellular machinery and that they diverge after the CD24+CD73+ maturity stage. [ABSTRACT FROM AUTHOR]

Published
2016
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168. Midline 1 directs lytic granule exocytosis and cytotoxicity of mouse killer T cells

Author

Boding, Lasse, primary, Hansen, Ann K., additional, Meroni, Germana, additional, Johansen, Bo B., additional, Braunstein, Thomas H., additional, Bonefeld, Charlotte M., additional, Kongsbak, Martin, additional, Jensen, Benjamin A. H., additional, Woetmann, Anders, additional, Thomsen, Allan R., additional, Ødum, Niels, additional, von Essen, Marina R., additional, and Geisler, Carsten, additional

Published
2014
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169. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

Author

Krejsgaard, Thorbjørn, primary, Willerslev-Olsen, Andreas, additional, Lindahl, Lise M., additional, Bonefeld, Charlotte M., additional, Koralov, Sergei B., additional, Geisler, Carsten, additional, Wasik, Mariusz A., additional, Gniadecki, Robert, additional, Kilian, Mogens, additional, Iversen, Lars, additional, Woetmann, Anders, additional, and Odum, Niels, additional

Published
2014
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171. IL-1β–Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity

Author

Nielsen, Morten M., primary, Lovato, Paola, additional, MacLeod, Amanda S., additional, Witherden, Deborah A., additional, Skov, Lone, additional, Dyring-Andersen, Beatrice, additional, Dabelsteen, Sally, additional, Woetmann, Anders, additional, Ødum, Niels, additional, Havran, Wendy L., additional, Geisler, Carsten, additional, and Bonefeld, Charlotte M., additional

Published
2014
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172. IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF)

Author

Willerslev-Olsen, Andreas, primary, Litvinov, Ivan V, additional, Fredholm, Simon M, additional, Petersen, David L, additional, Sibbesen, Nina A, additional, Gniadecki, Robert, additional, Zhang, Qian, additional, Bonefeld, Charlotte M, additional, Wasik, Mariusz A, additional, Geisler, Carsten, additional, Zhou, Youwen, additional, Woetmann, Anders, additional, Sasseville, Denis, additional, Krejsgaard, Thorbjørn, additional, and Ødum, Niels, additional

Published
2014
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173. Bacterial Toxins Fuel Disease Progression in Cutaneous T-Cell Lymphoma

Author

Willerslev-Olsen, Andreas, primary, Krejsgaard, Thorbjørn, additional, Lindahl, Lise, additional, Bonefeld, Charlotte, additional, Wasik, Mariusz, additional, Koralov, Sergei, additional, Geisler, Carsten, additional, Kilian, Mogens, additional, Iversen, Lars, additional, Woetmann, Anders, additional, and Odum, Niels, additional

Published
2013
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174. Validation of a diagnostic microRNA classifier in cutaneous T-cell lymphomas

Author

Marstrand, Troels, primary, Ahler, Charlotte B., additional, Ralfkiaer, Ulrik, additional, Clemmensen, Anders, additional, Kopp, Katharina L., additional, Sibbesen, Nina A., additional, Krejsgaard, Thorbjørn, additional, Litman, Thomas, additional, Wasik, Mariusz A., additional, Bonefeld, Charlotte M., additional, Grønbæk, Kirsten, additional, Gjerdum, Lise Mette Rahbek, additional, Gniadecki, Robert, additional, Ralfkiaer, Elisabeth, additional, Geisler, Carsten, additional, Woetmann, Anders, additional, Røpke, Mads A., additional, Glue, Christian, additional, Skov, Lone, additional, and Odum, Niels, additional

Published
2013
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175. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

Author

Kopp, Katharina, primary, Ralfkiaer, Ulrik, additional, Mette Gjerdrum, Lise, additional, Helvad, Rikke, additional, Pedersen, Ida, additional, Litman, Thomas, additional, Jønson, Lars, additional, Hagedorn, Peter, additional, Krejsgaard, Thorbjørn, additional, Gniadecki, Robert, additional, Bonefeld, Charlotte, additional, Skov, Lone, additional, Geisler, Carsten, additional, Wasik, Mariusz A., additional, Ralfkiaer, Elisabeth, additional, Ødum, Niels, additional, and Woetmann, Anders, additional

Published
2013
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177. PKC‐θ exists in an oxidized inactive form in naive human T cells

Author

von Essen, Marina Rode, primary, Kongsbak, Martin, additional, Levring, Trine Bøegh, additional, Hansen, Ann Kathrine, additional, Boding, Lasse, additional, Lauritsen, Jens Peter Holst, additional, Woetmann, Anders, additional, Baier, Gottfried, additional, Ødum, Niels, additional, Bonefeld, Charlotte Menné, additional, and Geisler, Carsten, additional

Published
2013
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179. Increased prevalence of lymphoid tissue inducer cells in the cerebrospinal fluid of patients with early multiple sclerosis.

Author

Degn, Matilda, Modvig, Signe, Dyring-Andersen, Beatrice, Bonefeld, Charlotte M., Frederiksen, Jette L., Geisler, Carsten, and von Essen, Marina R.

Subjects
LYMPHOID tissue, CEREBROSPINAL fluid, PATIENTS, MULTIPLE sclerosis, PATIENT compliance
Abstract

Background: Inflammatory cytokines produced by cells of the immune system are believed to play a central role in the pathogenesis of multiple sclerosis (MS). Innate lymphoid cells (ILCs) have been shown to produce and secrete a wide range of the cytokines involved in MS pathogenesis; however, a possible implication of ILCs in MS development and disease progression has not been investigated. Objective: With this study, we aimed to clarify a potential role of ILCs in the early stages of MS. Methods and Results: Using flow cytometry, we analysed the prevalence and phenotype of ILCs in the cerebrospinal fluid (CSF) of patients experiencing their first or second demyelinating event. We found a substantial increase in both frequency and number of ILCs, in particular the LTi subset, as compared to healthy controls. We also found an association between CSF pleocytosis and an increased frequency of LTi cells in the CSF, suggesting a favoured recruitment of blood derived LTi cells. Conclusion: Our data suggests a role for ILCs, and in particular the LTi subset, in the early stages of MS. This finding represents an important contribution to the understanding of early inflammation in MS, and adds new knowledge beneficial for future MS therapies. [ABSTRACT FROM AUTHOR]

Published
2016
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180. Vascular endothelial growth factor receptor-3 expression in mycosis fungoides

Author

Pedersen, Ida Holst, primary, Willerslev-Olsen, Andreas, additional, Vetter-Kauczok, Claudia, additional, Krejsgaard, Thorbjørn, additional, Lauenborg, Britt, additional, Kopp, Katharina Luise, additional, Geisler, Carsten, additional, Bonefeld, Charlotte M., additional, Zhang, Qian, additional, Wasik, Mariusz A., additional, Dabelsteen, Sally, additional, Woetmann, Anders, additional, Becker, Jurgen C., additional, and Odum, Niels, additional

Published
2012
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182. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Author

Ralfkiaer, Ulrik, primary, Hagedorn, Peter H., additional, Bangsgaard, Nannie, additional, Løvendorf, Marianne B., additional, Ahler, Charlotte B., additional, Svensson, Lars, additional, Kopp, Katharina L., additional, Vennegaard, Marie T., additional, Lauenborg, Britt, additional, Zibert, John R., additional, Krejsgaard, Thorbjørn, additional, Bonefeld, Charlotte M., additional, Søkilde, Rolf, additional, Gjerdrum, Lise M., additional, Labuda, Tord, additional, Mathiesen, Anne-Merete, additional, Grønbæk, Kirsten, additional, Wasik, Mariusz A., additional, Sokolowska-Wojdylo, Malgorzata, additional, Queille-Roussel, Catherine, additional, Gniadecki, Robert, additional, Ralfkiaer, Elisabeth, additional, Geisler, Carsten, additional, Litman, Thomas, additional, Woetmann, Anders, additional, Glue, Christian, additional, Røpke, Mads A., additional, Skov, Lone, additional, and Odum, Niels, additional

Published
2011
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183. Malignant Cutaneous T-Cell Lymphoma Cells Express IL-17 Utilizing the Jak3/Stat3 Signaling Pathway

Author

Krejsgaard, Thorbjørn, primary, Ralfkiaer, Ulrik, additional, Clasen-Linde, Erik, additional, Eriksen, Karsten W., additional, Kopp, Katharina L., additional, Bonefeld, Charlotte M., additional, Geisler, Carsten, additional, Dabelsteen, Sally, additional, Wasik, Mariusz A., additional, Ralfkiaer, Elisabeth, additional, Woetmann, Anders, additional, and Odum, Niels, additional

Published
2011
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186. Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells

Author

Eriksen, Karsten W., primary, Woetmann, Anders, additional, Skov, Lone, additional, Krejsgaard, Thorbjørn, additional, Bovin, Lone F., additional, Hansen, Mikkel L., additional, Grønbæk, Kirsten, additional, Billestrup, Nils, additional, Nissen, Mogens H., additional, Geisler, Carsten, additional, Wasik, Mariusz A., additional, and Ødum, Niels, additional

Published
2010
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188. TCR Down-Regulation Controls T Cell Homeostasis

Author

Boding, Lasse, primary, Bonefeld, Charlotte Menné, additional, Nielsen, Bodil L., additional, Lauritsen, Jens Peter H., additional, von Essen, Marina Rode, additional, Hansen, Ann Kathrine, additional, Larsen, Jeppe Madura, additional, Nielsen, Morten Milek, additional, Ødum, Niels, additional, and Geisler, Carsten, additional

Published
2009
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191. MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells.

Author

Boding, Lasse, Hansen, Ann K., Meroni, Germana, Levring, Trine B., Woetmann, Anders, Ødum, Niels, Bonefeld, Charlotte M., and Geisler, Carsten

Subjects
EXOCYTOSIS, CYTOTOXIC T cells, CYTOPLASMIC granules, UBIQUITIN ligases, GENE transfection
Abstract

We have recently shown that the E3 ubiquitin ligase midline 1 ( MID1) is upregulated in murine cytotoxic lymphocytes ( CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out ( MID1−/−) mice have a 25-30% reduction in exocytosis of lytic granules and cytotoxicity compared to CTL from wild-type ( WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1−/− CTL. Here, we showed that MID2, like MID1, is upregulated in activated murine T cells. Furthermore, MID1−/− CTL upregulated MID2 two-twenty-fold stronger than CTL from WT mice, suggesting that MID2 might compensate for MID1. In agreement, transfection of MID2 into MID1−/− CTL completely rescued exocytosis of lytic granules in MID1−/− CTL, and vice versa, knock-down of MID2 inhibited exocytosis of lytic granules in both WT and MID1−/− CTL, demonstrating that both MID1 and MID2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID1 and MID2 in CTL. [ABSTRACT FROM AUTHOR]

Published
2015
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192. Fine-tuning of T-cell development by the CD3γ di-leucine-based TCR-sorting motif.

Author

Lauritsen, Jens Peter H., Boding, Lasse, Buus, Terkild B., Kongsbak, Martin, Levring, Trine B., Rode, Anna K. O., Bonefeld, Charlotte Menné, and Geisler, Carsten

Subjects
T cell receptors, CD3 antigen, LEUCINE, PROTEIN kinase C, APOPTOSIS inhibition, GENETIC regulation
Abstract

The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down- regulation is abolished in thymocytes from CD3γLLAA mice with a mutated CD3γ diL motif, and that CD3γLLAA mice have reduced numbers of thymocytes compared with aged-matched wild-type mice. We found that early thymocyte development at the β-selection checkpoint is impaired resulting in reduced numbers of double negative (DN) 4 cells in CD3γLLAA mice. This was not caused by reduced proliferation but most probably by increased down-regulation of the antiapoptotic molecule Bcl-2 causing enhanced apoptosis during the transition from the DN3 to the DN4 stage. In contrast, proliferation of immature CD8 single positive (ISP) thymocytes was increased resulting in normal numbers of ISP in CD3γLLAA mice. Despite the normal numbers of ISP, CD3γLLAA mice had reduced numbers of double positive and SP thymocytes indicating that the CD3γ diL motif also affected later stages of T-cell development. In accordance, we found that positive and negative selection, differentiation toward CD4 and CD8 SP T cells and the development of nonconventional T cells were affected in CD3γLLAA mice. In conclusion, our study identifies an important role of the CD3γ diL motif in T-cell development most probably mediated by its fine-tuning of pre-TCR and TCR expression, down-regulation and signaling. [ABSTRACT FROM AUTHOR]

Published
2015
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193. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro.

Author

Feng, Shan, Madsen, Suzi H., Viller, Natasja N., Neutzsky‐Wulff, Anita V., Geisler, Carsten, Karlsson, Lars, and Söderström, Kalle

Subjects
INTERLEUKIN-15, KILLER cells, OSTEOCLAST inhibition, LYMPHOCYTE function-associated antigen-1, RHEUMATOID arthritis, IN vitro studies, VIRUS diseases, APOPTOSIS, PATIENTS
Abstract

Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer ( NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow as well as to inflammatory sites associated with enhanced bone erosion, including the joints of patients with rheumatoid arthritis, little is known about the impact NK cells may have on mature osteoclasts and bone erosion. We studied the interaction between human NK cells and autologous monocyte-derived osteoclasts from healthy donors in vitro. We show that osteoclasts express numerous ligands for receptors present on activated NK cells. Co-culture experiments revealed that interleukin-15-activated, but not resting, NK cells trigger osteoclast apoptosis in a dose-dependent manner, resulting in drastically decreased bone erosion. Suppression of bone erosion requires contact between NK cells and osteoclasts, but soluble factors also play a minor role. Antibodies masking leucocyte function-associated antigen-1, DNAX accessory molecule-1 or tumour necrosis factor-related apoptosis-inducing ligand enhance osteoclast survival when co-cultured with activated NK cells and restore the capacity of osteoclasts to erode bone. These results suggest that interleukin-15-activated NK cells may directly affect bone erosion under physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Published
2015
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194. Midline 1 controls polarization and migration of murine cytotoxic T cells.

Author

Boding, Lasse, Hansen, Ann K., Nielsen, Morten M., Meroni, Germana, Braunstein, Thomas H., Woetmann, Anders, Ødum, Niels, Bonefeld, Charlotte M., and Geisler, Carsten

Subjects
CYTOTOXIC T cells, MICROTUBULES, EMBRYOLOGY, ALLERGIES, EXOCYTOSIS, UROPODA
Abstract

Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims of the present study were to determine the localization of MID1 in migrating CTLs, and to investigate whether MID1 affects CTL polarization and migration. We found that MID1 mainly localizes to the uropod of migrating CTLs and that it has a substantial impact on CTL polarization and migration in vitro. Furthermore, analysis of contact hypersensitivity responses supported that MID1 controls effector functions of CTLs in hapten-challenged skin in vivo. These results provide significant new knowledge on the role of MID1 in CTL biology. [ABSTRACT FROM AUTHOR]

Published
2015
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195. Epicutaneous exposure to nickel induces nickel allergy in mice via a MyD88-dependent and interleukin-1-dependent pathway.

Author

Vennegaard, Marie T., Dyring‐Andersen, Beatrice, Skov, Lone, Nielsen, Morten M., Schmidt, Jonas D., Bzorek, Michael, Poulsen, Steen S., Thomsen, Allan R., Woetmann, Anders, Thyssen, Jacob P., Johansen, Jeanne D., Ødum, Niels, Menné, Torkil, Geisler, Carsten, and Bonefeld, Charlotte M.

Subjects
NICKEL, ANIMAL models in research, ALLERGIES, INTRADERMAL injections, T cells
Abstract

Background Several attempts to establish a model in mice that reflects nickel allergy in humans have been made. Most models use intradermal injection of nickel in combination with adjuvant to induce nickel allergy. However, such models poorly reflect induction of nickel allergy following long-lasting epicutaneous exposure to nickel. Objective To develop a mouse model reflecting nickel allergy in humans induced by epicutaneous exposure to nickel, and to investigate the mechanisms involved in such allergic responses. Methods Mice were exposed to NiCl2 on the dorsal side of the ears. Inflammation was evaluated by the swelling and cell infiltration of the ears. T cell responses were determined as numbers of CD4+ and CD8+ T cells in the draining lymph nodes. Localization of nickel was examined by dimethylglyoxime staining. Results Epicutaneous exposure to nickel results in prolonged localization of nickel in the epidermis, and induces nickel allergy in mice. The allergic response to nickel following epicutaneous exposure is MyD88-dependent and interleukin ( IL)-1 receptor-dependent, but independent of toll-like receptor ( TLR)-4. Conclusion This new model for nickel allergy that reflects epicutaneous exposure to nickel in humans shows that nickel allergy is dependent on MyD88 and IL-1 receptor signalling, but independent of TLR4. [ABSTRACT FROM AUTHOR]

Published
2014
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198. Constitutive and Ligand-Induced TCR Degradation

Author

von Essen, Marina, primary, Bonefeld, Charlotte Menné, additional, Siersma, Volkert, additional, Rasmussen, Anette Bødker, additional, Lauritsen, Jens Peter H., additional, Nielsen, Bodil L., additional, and Geisler, Carsten, additional

Published
2004
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199. Bi-phasic Effect of Interferon (IFN)-α

Author

Eriksen, Karsten Wessel, primary, Sommer, Viveca Horst, additional, Woetmann, Anders, additional, Rasmussen, Anette Bødker, additional, Brender, Christine, additional, Svejgaard, Arne, additional, Skov, Søren, additional, Geisler, Carsten, additional, and Ødum, Niels, additional

Published
2004
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