Article
Oncology
Chella Krishna Vadivel, Maria Gluud, Sara Torres-Rusillo, Lasse Boding, Andreas Willerslev-Olsen, Terkild B. Buus, Tea Kirkegaard Nielsen, Jenny L. Persson, Charlotte M. Bonefeld, Carsten Geisler, Thorbjorn Krejsgaard, Anja T. Fuglsang, Niels Odum, Anders Woetmann
Summary: This study demonstrates the nuclear localization of JAK3 in malignant T cells and its interactions with key nuclear proteins, suggesting a novel non-canonical role in cutaneous T cell lymphoma.
Review
Medicine, General & Internal
Kamran Ghoreschi, Anna Balato, Charlotta Enerback, Robert Sabat
Summary: Psoriasis is a chronic inflammatory disease affecting 2-3% of the global population, characterized by sharply demarcated erythematous and scaly skin lesions. The disease results from hyperproliferation and disturbed differentiation of epidermal keratinocytes provoked by immune mediators of the IL-23 and IL-17 pathway. Therapeutics targeting IL-23, IL-17, and IL-17RA have shown excellent efficacy in treating psoriasis.
Article
Cell Biology
Loka Reddy Velatooru, Cheng Hui Hu, Pedram Bijani, Xiaohong Wang, Pierr Bojaxhi, Hao Chen, Madeleine Duvic, Xiao Ni
Summary: In this study, a novel JAK3-INSL3 fusion transcript was identified in cutaneous T-cell lymphomas (CTCL). Higher expression of JAK3-INSL3 was associated with poorer survival in CTCL patients. Knockdown of JAK3-INSL3 decreased cell proliferation and tumor growth.
Article
Chemistry, Medicinal
Amira M. Badr, Layla A. Alkharashi, Iman O. Sherif, Alaa A. Alanteet, Hind N. Alotaibi, Yasmen F. Mahran
Summary: This study found that thymol can counteract 5-FU-induced intestinal mucositis by modulating the activity of the IL-17/Notch1/STAT3 pathway. Additionally, thymol enhances the antiproliferative action of 5-FU on cancer cells.
Article
Cell Biology
Pengyu Zhang, Qiang Zhang, Zhenxia Shao
Summary: This study found that the expression of S1PR4 was significantly increased in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). Silencing S1PR4 could decrease the proliferation, migration, and proinflammation of RA-FLSs, and promote apoptosis. These effects might be achieved by repressing the interleukin-17 (IL-17)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.
Article
Biochemistry & Molecular Biology
Mariko Komuro, Masaki Nagane, Tomoki Fukuyama, Xiaolin Luo, Shinobu Hiraki, Masakatsu Miyanabe, Miyuki Ishikawa, Chiaki Niwa, Hironobu Murakami, Mariko Okamoto, Tadashi Yamashita
Summary: The study found that sphingomyelin plays a vital role in maintaining the cutaneous barrier through regulation of the STAT3 pathway. These results suggest that sphingomyelin could be a potential therapeutic target for treating dermatitis.
Review
Immunology
Claudia Schinocca, Chiara Rizzo, Serena Fasano, Giulia Grasso, Lidia La Barbera, Francesco Ciccia, Giuliana Guggino
Summary: IL-23 is a pro-inflammatory cytokine composed of two subunits and has a key role in protective immune response, but dysregulation can exacerbate chronic immune-mediated inflammation. Activation of the IL-23/IL-17 axis contributes to the development of various inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hanqing Zhao, Xin Guo, Yunxuan Lei, Wenjie Xia, Feiyang Cai, Dehao Zhu, Yang An, Yebin Xi, Xiaoyin Niu, Zhaojun Wang, Tao Yue, Guangjie Chen
Summary: This study demonstrated the inhibitory effects of gamma-Tocotrienol (GT3) on Th17 differentiation and function through the suppression of STAT3 signaling pathway both in vitro and in vivo. GT3 may have potential therapeutic effects in treating Th17-related diseases.
MOLECULAR IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yu Sawada, Ayako Setoyama, Yumiko Sakuragi, Natsuko Saito-Sasaki, Haruna Yoshioka, Motonobu Nakamura
Summary: The skin is exposed to various environmental stimuli, leading to inflammatory immune responses, especially towards cutaneous fungal infections. IL-17 producing cells play a crucial role in anti-fungal action, but their actual impact remains unclear. Research focuses on the role of IL-17-producing cells in cutaneous fungal infections and characteristics of infectious fungi on the skin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Johannes Wohlrab, Dennis Gerloff, Kathleen Gebhardt
Summary: The key players in chronic inflammatory skin diseases are cytokines belonging to the IL-17 group, IL-17 receptors and Th17 cells. Studies have shown that IL-17RA is the most abundantly expressed receptor type in various cutaneous cell types from healthy human subjects. Different IL-17 subtypes have varying effects on the expression of different receptor types, suggesting the need for further research on relevant co-stimulating factors under physiological and pathophysiological conditions.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Shuichi Nakai, Eiji Kiyohara, Rei Watanabe
Summary: CTCL is a heterogeneous group of non-Hodgkin lymphoma, mainly including MF and SS, with malignant cells possibly originating from different T cell phenotypes. The pathogenesis and therapeutic strategies for CTCL remain unclear due to the similar characteristics between malignant cells and anti-tumor T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jihye Yoo, Darong Kim, Jiyoung Park, Young-Kook Kim, Hea-Young Park Choo, Hyun Ae Woo
Summary: Development of small molecule inhibitors for inflammatory cytokines is a promising strategy for treating inflammatory diseases like rheumatoid arthritis. The synthesized compounds demonstrated significant inhibitory activity on interleukins and their signaling pathways, showing potential for further development as small molecule inhibitors for RA.
Article
Immunology
Xiaoman Guo, Xinru Mao, Di Tian, Yixin Liao, Bintao Su, Chaoliang Ye, Dongling Shi, Tie Fu Liu, Yun Ling, Yi Hao
Summary: Cryptococcus neoformans infection in the central nervous system leads to high levels of IL-17 production, mainly by CD4(+) T cells, and is dependent on STAT3 signaling. IL-17 could serve as a diagnostic biomarker for C. neoformans infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Bei Huang, Xiaoling Lang, Xihong Li
Summary: This article focuses on the role of interleukin-6 (IL-6) in liver cancer, breast cancer, colorectal cancer, gastric cancer, lung cancer, pancreatic cancer and ovarian cancer, as well as its relationship with the JAK2/STAT3 signaling pathway.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Tariq N. Aladily, Tasnim Abushunar, Ahmad Alhesa, Raneen Alrawi, Noor Almaani, Maram Abdaljaleel
Summary: The morphologic changes in early-stage mycosis fungoides (MF) may overlap with benign inflammatory dermatitis (BID). Immunohistochemical stains alone cannot discriminate between MF and BID, but the double expression of TOX and IL-17 may support the diagnosis of MF.
Article
Allergy
Anders B. Funch, Veronika Mraz, Anne-Sofie O. Gadsboll, Mia H. Jee, Julie F. Weber, Niels Odum, Anders Woetmann, Jeanne D. Johansen, Carsten Geisler, Charlotte M. Bonefeld
Summary: This study demonstrates that epidermal CD8(+) T-RM cells play a crucial role in causing ACD flare-ups through rapid recruitment of neutrophils to the epidermis.
Article
Chemistry, Analytical
Noortje de Haan, Yoshiki Narimatsu, Mikkel Koed Moller Aasted, Ida S. B. Larsen, Irina N. Marinova, Sally Dabelsteen, Sergey Y. Vakhrushev, Hans H. Wandall
Summary: In this study, a high-throughput sample preparation method was developed for the nonreductive release and characterization of O-glycans from human cell materials. By using reducing-end labeling and mass spectrometry analysis, O-glycan structural isomers in complex mixtures were efficiently separated and detected. This method provides an opportunity to study glycomic changes in human tissue and disease models using mainstream analytical equipment.
ANALYTICAL CHEMISTRY
(2022)
Article
Hematology
Maria Gluud, Emil M. H. Pallesen, Terkild B. Buus, Lise Mette Rahbek Gjerdrum, Lise M. Lindahl, Maria R. Kamstrup, Michael Bzorek, Maria Danielsen, Rikke Bech, Madalena N. Monteiro, Edda Blumel, Andreas Willerslev-Olsen, Anders Lykkebo-Valloe, Chella Krishna Vadivel, Thorbjorn Krejsgaard, Charlotte Menne Bonefeld, Carsten Geisler, Juergen C. Becker, Sergei B. Koralov, Lars Iversen, Thomas Litman, Anders Woetmann, Niels Odum
Summary: 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 and increase the risk of bacterial infection. The study found that malignant T cells secrete cytokines that downregulate the expression of filaggrin and filaggrin-2, leading to compromised skin barrier. Treatment with JAK inhibitors can reverse this effect and increase filaggrin expression in patients with advanced CTCL.
Article
Dentistry, Oral Surgery & Medicine
Sune Demant, Ton Schoenmaker, Sophie M. G. van Erck, Sally Dabelsteen, Teun J. de Vries, Lars Bjorndal
Summary: The formation of dense connective tissue within the dental pulp and its association with pulpal inflammation in teeth with advanced carious lesions were investigated in this study. In addition, the study investigated whether inflammation affects the expression of markers related to chondrogenesis/osteogenesis in pulp cells in vitro.
INTERNATIONAL ENDODONTIC JOURNAL
(2022)
Article
Multidisciplinary Sciences
Mathias Nielsen, Noortje de Haan, Weston Kightlinger, Zilu Ye, Sally Dabelsteen, Minyan Li, Michael C. Jewett, Ieva Bagdonaite, Sergey Y. Vakhrushev, Hans H. Wandall
Summary: This study systematically analyzed the isoform-specific targets of all GalNAc-Ts expressed in skin cells, revealing the biological effects of O-glycan initiation on epithelial formation. Over 300 unique glycosylation sites were identified on a diverse set of proteins, regulated by specific GalNAc-T isoforms, highlighting their impact on tissue phenotypes. The variability in O-glycosylation site-occupancy of secreted proteins suggests the importance of individual O-glycosylation sites in driving biological functions.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Anna K. O. Rode, Terkild Brink Buus, Veronika Mraz, Fatima Abdul Hassan Al-Jaberi, Daniel Villalba Lopez, Shayne L. Ford, Stephanie Hennen, Ina Primon Eliasen, Ib Vestergaard Klewe, Leila Gharehdaghi, Adrian Dragan, Mette M. Rosenkilde, Anders Woetmann, Lone Skov, Niels Odum, Charlotte M. Bonefeld, Martin Kongsbak-Wismann, Carsten Geisler
Summary: Studies show that activated human T cells express functional GLP-1R, with a pronounced expression in induced Treg cells. Through single-cell sequencing, the presence of GLP-1R in iTreg cells was confirmed.
Article
Biochemistry & Molecular Biology
Zilu Ye, Gulcan Kilic, Sally Dabelsteen, Irina N. Marinova, Jens F. B. Thofner, Ming Song, Asha M. Rudjord-Levann, Ieva Bagdonaite, Sergey Y. Vakhrushev, Cord H. Brakebusch, Jesper v Olsen, Hans H. Wandall
Summary: This study investigates the importance of TGF-beta signaling pathway in human epithelial tissue homeostasis and transformation. Using genetic engineering, 3D tissue models, and quantitative proteomics, the study reveals that the loss of TGF-beta signaling promotes cell proliferation, delays differentiation, and induces invasive growth. The loss of TGF-beta receptor II (TGF-beta RII) has a stronger impact on cell proliferation and differentiation, and it also affects cell-matrix interactions and activates proinflammatory mediators.
Article
Allergy
Anders Boutrup Funch, Julie Friis Weber, Rebecca Kitt Davidson Lohmann, Veronika Mraz, Kelvin Yeung, Mia Hamilton Jee, Niels Odum, Anders Woetmann, Jeanne Duus Johansen, Carsten Geisler, Charlotte Menne Bonefeld
Summary: This study reveals that clinically relevant contact allergens can generate pathogenic, epidermal CD8(+) T-RM cells that recruit neutrophils following re-exposure to the allergen, but this response is normally suppressed by the induction of anti-inflammatory CD4(+) T cells.
CONTACT DERMATITIS
(2023)
Article
Biochemistry & Molecular Biology
Kelly Cristina Gomes Manfrere, Marina Passos Torrealba, Frederico Moraes Ferreira, Emanuella Sarmento Alho de Sousa, Denis Miyashiro, Franciane Mouradian Emidio Teixeira, Ricardo Wesley Alberca Custodio, Helder I. Nakaya, Yasmin Alefe Leuzzi Ramos, Mirian Nacagami Sotto, Anders Woetmann, Niels odum, Alberto Jose da Silva Duarte, Jose Antonio Sanches, Maria Notomi Sato
Summary: This study investigated the expression levels of inflammatory markers IL-1B and IL-18 in the skin, serum, blood cells, and lymph nodes of patients with Sezary syndrome, as potential markers of inflammasome activation. The findings showed compartmentalized expressions of IL-1B and IL-18, with increased expression of IL-1B in the epidermis and increased expression of IL-18 in the dermis. In advanced stages of the disease, enhanced expression of IL-18 and downregulation of IL-1B were observed in the lymph nodes. This study provided the first evidence of the imbalance of IL-1B and IL-18 in patients with Sezary syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Allergy
Veronika Mraz, Anders B. Funch, Mia H. Jee, Anne-Sofie O. Gadsboll, Julie F. Weber, Kelvin Yeung, Rebecca K. D. Lohmann, Alana Hawkes, Niels Odum, Anders Woetmann, Dianne Mckay, Deborah Witherden, Carsten Geisler, Charlotte M. Bonefeld
Summary: CD8(+) TRM cells play a key role in allergic contact dermatitis (ACD), and CD100 is an essential protein for the activation of CD8(+) TRM cells and the flare-up response of ACD.
CONTACT DERMATITIS
(2023)
Article
Allergy
Veronika Mraz, Rebecca K. D. Lohmann, Mandy Menzel, Alana Hawkes, Helen Vaher, Anders B. Funch, Mia H. Jee, Anne-Sofie o. Gadsboll, Julie F. Weber, Kelvin Yeung, Niels Odum, Anders Woetmann, Dianne Mckay, Deborah Witherden, Carsten Geisler, Charlotte M. Bonefeld
Summary: This study reveals the central role of JAML in CHS and suggests a potential new target for the treatment of ACD in humans.
CONTACT DERMATITIS
(2023)
Article
Multidisciplinary Sciences
Asha M. Rudjord-Levann, Zilu Ye, Lise Hafkenscheid, Sabrina Horn, Renske Wiegertjes, Mathias A. I. Nielsen, Ming Song, Caroline B. K. Mathiesen, Jesse Stoop, Sean Stowell, Per Thor Straten, Hakon Leffler, Sergey Y. Vakhrushev, Sally Dabelsteen, Jesper V. Olsen, Hans H. Wandall
Summary: By analyzing the expression of galectin-1, we found that it is upregulated in the extracellular matrix of multiple tumors. Further proteomic and phosphoproteomic analysis revealed that galectin-1 induces a tumor-associated macrophage phenotype with increased expression of PD-L1 and IDO1. Galectin-1 also stimulates IDO1 production through JAK/STAT signaling. The cellular source of galectin-1 in the extracellular matrix was identified as epithelial and stromal cells. Targeting galectin-1 has potential in immunotherapeutic treatment of human cancers.
Meeting Abstract
Oncology
Mikkel K. M. Aasted, Aaron C. Groen, John T. Keane, Sally Dabelsteen, Edwin Tan, Julia Schnabel, Fang Liu, Hyeon-Gyu S. Lewis, Constantine Theodoropulos, Avery D. Posey, Hans H. Wandall
Article
Biochemistry & Molecular Biology
Troels Boldt Romer, Fawzi Khoder-Agha, Mikkel Koed Moller Aasted, Noortje de Haan, Sabrina Horn, August Dylander, Tao Zhang, Emil Marek Heymans Pallesen, Sally Dabelsteen, Manfred Wuhrer, Christine Flodgaard Hogsbro, Emil Aagaard Thomsen, Jacob Giehm Mikkelsen, Hans H. Wandall
Summary: This study reveals the mechanism behind the regulation of cancer-associated O-glycan expression by ZIP9 and zinc ions. Deletion of the ZIP9 gene or accumulation of zinc ions leads to cancer-like glycosylation, while overexpression of COSMC mitigates these changes.
Meeting Abstract
Biochemistry & Molecular Biology
Fawzi Khoder-Agha, Ming Song, Magnus T. Borre, Irina Nikolaeva Marinova, Zilu Ye, Stine Falsig Pedersen, Sally Dabelsteen, Hans H. Wandall