Article
Multidisciplinary Sciences
Jie Cheng, Timothy G. Myers, Callie Levinger, Princy Kumar, Jai Kumar, Bruktawit A. Goshu, Alberto Bosque, Marta Catalfamo
Summary: IL-27 has been shown to inhibit HIV replication and enhance the function of HIV-specific T cells. It activates STAT1 and modulates T-bet expression, leading to increased IFNγ secretion in HIV-specific T cells.
Article
Biochemistry & Molecular Biology
Sihan Wu, Rui Ma, Yajie Zhong, Zilin Chen, Hongyan Zhou, Minyi Zhou, Waipo Chong, Jun Chen
Summary: IL-27 signaling plays a suppressive role in regulating uveitogenic Th1/Th17 responses in EAU, with deficiency exacerbating ocular inflammation and impairing visual function. It also affects multiple CD4(+) cell subsets, including effector Th1 and Th17 cells, and regulatory Tr1 cells, indicating therapeutic potential in controlling uveitis through enhancing IL-27 signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yanyu Zhang, Song Gao, Shifei Yao, Danlin Weng, Yan Wang, Qi Huang, Xuemei Zhang, Hong Wang, Wenchun Xu
Summary: The study found that the SPY1 vaccine increased the expression of IL-27 and its specific receptor (WSX-1), promoting vaccine protection through activation of the STAT3 and NF-κB signaling pathways and production of memory CD4(+)T cells to enhance Th17 cell polarization. Additionally, the immune protection of the vaccine was independent of aerobic glycolysis.
Article
Immunology
Chia-Hao Lin, Cheng-Jang Wu, Sunglim Cho, Rasika Patkar, William J. Huth, Ling-Li Lin, Mei-Chi Chen, Elisabeth Israelsson, Joanne Betts, Magdalena Niedzielska, Shefali A. Patel, Han G. Duong, Romana R. Gerner, Chia-Yun Hsu, Matthew Catley, Rose A. Maciewicz, Hiutung Chu, Manuela Raffatellu, John T. Chang, Li-Fan Lu
Summary: This study reveals that intestinal T-reg cells produce IL-27 to regulate T(H)17 cell immunity, leading to exacerbated intestinal inflammation and colitis-associated cancer, but also providing protection against enteric bacterial infection. A CD83(+)CD62L(lo) T-reg cell subset is identified as the main IL-27 producer.
Editorial Material
Immunology
Emily R. Siniscalco, Joe Craft
Summary: Regulatory T cells produce IL-27 to restrain TH17 cell-mediated immune responses in the intestine, effectively limiting autoimmune inflammation and T cell responses to specific gut pathogens.
Article
Biology
Nathanael A. Caveney, Caleb R. Glassman, Kevin M. Jude, Naotaka Tsutsumi, K. Christopher Garcia
Summary: Interleukin 27 (IL-27) is a heterodimeric cytokine that plays an important role in immune homeostasis. This study used cryogenic-electron microscopy to determine the quaternary structure of IL-27 and its receptor complex, providing insights into the receptor assembly mechanism and distinguishing it from related cytokines.
Article
Immunology
Eigo Kawahara, Mitsuki Azuma, Hiroyuki Nagashima, Koki Omori, Sho Akiyama, Yuka Fujimori, Mayu Oishi, Nagito Shibui, Kosuke Kawaguchi, Masashi Morita, Yuko Okuyama, Naoto Ishii, Takanori So
Summary: TRAFS acts as a negative regulator for IL-6 receptor signaling and a positive regulator for GITR-mediated signaling in CD4(+) T cells. It limits the signaling via the IL-27 receptor and promotes the proliferation of CD4(+) T cells. The regulatory activity of TRAF5 in gp130 is distinct from its activity in TNF receptor family molecules in T cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Liang Zhang, Manli Liu, Wenhua Liu, Chaojie Hu, Hongqi Li, Jie Deng, Qi Cao, Yiping Wang, Wei Hu, Qing Li
Summary: Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. The authors explored the role of IL-17A on endothelial cell senescence and its associated signaling pathways. Their data reveals a previously unsuspected link between IL-17A and endothelial cell senescence, mediated by the NF-kappa B /p53/Rb signaling pathway.
LABORATORY INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Lu Yang, Na Li, Di Yang, Anwei Chen, Jianlong Tang, Yukai Jing, Danqing Kang, Panpan Jiang, Xin Dai, Li Luo, Qiuyue Chen, Jiang Chang, Ju Liu, Heng Gu, Yanmei Huang, Qianglin Chen, Zhenzhen Li, Yingzi Zhu, Heather Miller, Yan Chen, Liru Qiu, Heng Mei, Yu Hu, Quan Gong, Chaohong Liu
Summary: The study revealed that deficiency of CCL2 enhances BCR signaling, leading to reduced marginal zone B cells and increased germinal center B cells, which can be rescued by mTORC1 inhibition. Additionally, CCL2 deficiency also promotes early activation of B cells.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Multidisciplinary Sciences
Joachim Hanna, Flavio Beke, Louise M. O'Brien, Chrysa Kapeni, Hung-Chang Chen, Valentina Carbonaro, Alexander B. Kim, Kamal Kishore, Timon E. Adolph, Mikkel-Ole Skjoedt, Karsten Skjoedt, Marc de la Roche, Maike de la Roche
Summary: The study implicates Hedgehog signaling in Th17 polarization and intestinal immunopathology, suggesting the potential therapeutic use of Hedgehog inhibitors in the treatment of inflammatory bowel disease.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Brandon W. Lewis, Devine Jackson, Stephanie A. Amici, Joshua Walum, Manel Guessas, Sonia Guessas, Elise Coneglio, Akhila V. Boda, Mireia Guerau-de-Arellano, Mitchell H. Grayson, Rodney D. Britt
Summary: The increase in Th1 inflammation is associated with a decrease in corticosteroid sensitivity in severe asthma, but increased airway pathology and airway hyperresponsiveness still persist in the absence of STAT1, indicating corticosteroid insensitivity in structural airway cells is a process independent of STAT1.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hye-Soo Park, Seunga Choi, Yong-Woo Back, Kang-In Lee, Han-Gyu Choi, Hwa-Jung Kim
Summary: The study found that PGE2 produced by RpfE-activated dendritic cells via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor, contributing to defense against Mycobacterium tuberculosis infection. Moreover, adding optimal amount of PGE2 to IL-2-IL-6-IL-23p19-IL-1 beta is essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yibo Jin, Paul K. Fyfe, Scott Gardner, Stephan Wilmes, Doryen Bubeck, Ignacio Moraga
Summary: IL-27 is an important cytokine that induces immunosuppressive responses. The study reveals the structure of the IL-27 receptor recognition complex and provides insights into the mechanism of IL-27 signaling. These findings contribute to a better understanding of IL-27's function and regulation.
Article
Cell Biology
Kathryne E. Marks, Stephanie Flaherty, Kristen M. Patterson, Matthew Stratton, Gustavo J. Martinez, Joseph M. Reynolds
Summary: The study shows that activation of TLR2 increases the pathogenicity and migratory capacity of Th17 cells, comparable to IL-23. RNA sequencing revealed differential expression of genes associated with Th17 pathogenicity through the TLR2 pathway, including Ipcef1.
Article
Biology
Dong Hyun Kim, Hee Young Kim, Sunjung Cho, Su-Jin Yoo, Won-Ju Kim, Hye Ran Yeon, Kyungho Choi, Je-Min Choi, Seong Wook Kang, Won-Woo Lee
Summary: The study demonstrates the crucial role of IL-1RII receptor in regulating IL-17 responses, affecting the functionality of CD4(+) T cells by limiting IL-1 beta responsiveness.
Article
Biochemistry & Molecular Biology
Jonas Loetscher, Adria-Arnau Marti Lindez, Nicole Kirchhammer, Elisabetta Cribioli, Greta Maria Paola Giordano Attianese, Marcel P. Trefny, Markus Lenz, Sacha Rothschild, Paolo Strati, Marco Kuenzli, Claudia Lotter, Susanne H. Schenk, Philippe Dehio, Jordan Loeliger, Ludivine Litzler, David Schreiner, Victoria Koch, Nicolas Page, Dahye Lee, Jasmin Graehlert, Dmitry Kuzmin, Anne-Valerie Burgener, Doron Merkler, Miklos Pless, Maria L. Balmer, Walter Reith, Joerg Huwyler, Melita Irving, Carolyn G. King, Alfred Zippelius, Christoph Hess
Summary: This study reveals the importance of extracellular magnesium in cellular immunity, particularly in the activation of the co-stimulatory molecule LFA-1. The findings demonstrate that magnesium-sufficiency enhances the function of immune cells and the effectiveness of T cell therapies. Low serum magnesium levels are associated with disease progression and reduced overall survival in patients receiving CAR T cell and immune checkpoint antibody treatments.
Article
Biochemistry & Molecular Biology
Cedric O. Renaud, Panos G. Ziros, Amandine Mathias, Caroline Pot, Gerasimos P. Sykiotis
Summary: A retrospective observational study on 163 MS patients treated with DMF showed a very low incidence of functional TD, with most cases diagnosed before DMF treatment. The good thyroid tolerance of DMF argues against screening for TD in MS patients considered for or treated with DMF. Further study of Nrf2 activators for the prevention and treatment of TD is supported.
Article
Clinical Neurology
S. Borrelli, A. Mathias, G. Le Goff, R. Du Pasquier, M. Theaudin, C. Pot
Summary: Dimethyl fumarate treatment can lead to lymphopenia and has a long-term impact on lymphocyte biology even after discontinuation. When switching therapies, the risk of opportunistic infections should be considered.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Multidisciplinary Sciences
Nicola Rothammer, Marcel S. Woo, Simone Bauer, Lars Binkle-Ladisch, Giovanni Di Liberto, Kristof Egervari, Ingrid Wagner, Undine Haferkamp, Ole Pless, Doron Merkler, Jan Broder Engler, Manuel A. Friese
Summary: Neuroinflammation induces the expression of histone methyltransferase G9a, which promotes neuronal vulnerability to inflammation by repressing anti-ferroptotic genes and triggering ferroptosis. Inhibition of G9a activity restores anti-ferroptotic gene expression, reduces inflammation-induced neuronal loss, and improves clinical outcome. G9a inhibition also enhances anti-ferroptotic gene expression in human neuronal cultures. Therefore, G9a is a potential therapeutic target for countering inflammation-induced neurodegeneration.
Article
Endocrinology & Metabolism
Maria Papageorgiou, Emmanuel Biver, Julie Mareschal, Nicholas Edward Phillips, Alexandra Hemmer, Emma Biolley, Nathalie Schwab, Emily N. C. Manoogian, Elena Gonzalez Rodriguez, Daniel Aeberli, Didier Hans, Caroline Pot, Satchidananda Panda, Nicolas Rodondi, Serge L. Ferrari, Tinh-Hai Collet
Summary: This study investigated the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. The results showed that TRE had no detrimental effects on bone health in the overall population, but in weight loss responders, it was associated with some bone-sparing effects compared with SDA.
Article
Clinical Neurology
Andreas Agrafiotis, Raphael Dizerens, Ilena Vincenti, Ingrid Wagner, Raphael Kuhn, Danielle Shlesinger, Marcos Manero-Carranza, Tudor-Stefan Cotet, Kai-Lin Hong, Nicolas Page, Nicolas Fonta, Ghazal Shammas, Alexandre Mariotte, Margot Piccinno, Mario Kreutzfeldt, Benedikt Gruntz, Roy Ehling, Alessandro Genovese, Alessandro Pedrioli, Andreas Dounas, Soeren Franzenburg, Hayrettin Tumani, Tania Kuempfel, Vladyslav Kavaka, Lisa Ann Gerdes, Klaus Dornmair, Eduardo Beltran, Annette Oxenius, Sai T. T. Reddy, Doron Merkler, Alexander Yermanos
Summary: B cells play a role in the development of inflammatory diseases in the central nervous system (CNS) through various mechanisms. In this study, B cells from murine models of viral infections and autoimmunity in the CNS were profiled. It was found that there is a population of clonally expanded, antibody-secreting cells that respond to viral antigens and persist in the brain even after infection is resolved. Similar populations were also detected in relapsing multiple sclerosis patients.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Florian Ruiz, Benjamin Peter, Jessica Rebeaud, Solenne Vigne, Valentine Bressoud, Martin Roumain, Tania Wyss, Yannick Yersin, Ingrid Wagner, Mario Kreutzfeldt, Marisa Pimentel Mendes, Camille Kowalski, Gael Boivin, Leonard Roth, Markus Schwaninger, Doron Merkler, Giulio G. Muccioli, Stephanie Hugues, Tatiana Petrova, Caroline Pot
Summary: The vasculature plays a critical role in regulating leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases such as multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses is still unclear. This study investigates the role of Cholesterol-25-hydroxylase (Ch25h)-derived bioactive lipids in promoting neuroinflammation and reveals that Ch25h deficiency in CNS endothelial cells attenuates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
Article
Clinical Neurology
Stephanie Meier, Eline A. J. Willemse, Sabine Schaedelin, Johanna Oechtering, Johannes Lorscheider, Lester Melie-Garcia, Alessandro Cagol, Muhamed Barakovic, Riccardo Galbusera, Suvitha Subramaniam, Christian Barro, Ahmed Abdelhak, Simon Thebault, Lutz Achtnichts, Patrice Lalive, Stefanie Muller, Caroline Pot, Anke Salmen, Giulio Disanto, Chiara Zecca, Marcus D'Souza, Annette Orleth, Michael Khalil, Arabella Buchmann, Renaud Du Pasquier, Ozgur Yaldizli, Tobias Derfuss, Klaus Berger, Marco Hermesdorf, Heinz Wiendl, Fredrik Piehl, Marco Battaglini, Urs Fischer, Ludwig Kappos, Claudio Gobbi, Cristina Granziera, Claire Bridel, David Leppert, Aleksandra Maleska Maceski, Pascal Benkert, Jens Kuhle
Summary: This study found that serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) are correlated with features of disease progression in multiple sclerosis (MS) and can predict disease progression. sGFAP may serve as a useful biomarker for disease progression in MS in individual patient management and drug development.
Article
Clinical Neurology
Amandine Mathias, Vasiliki Pantazou, Sylvain Perriot, Mathieu Canales, Samuel Jones, Larise Oberholster, Michael Moulin, Craig Fenwick, Raphael Bernard-Valnet, Marie Theaudin, Caroline Pot, Renaud A. Du Pasquier
Summary: This study aims to investigate the impact of ocrelizumab (OCRE) on immune cell subsets in patients with multiple sclerosis (pwMS). The results showed that OCRE not only depletes B cells, but also reduces memory CD8(+) T cells, which may increase the risk of infections. Therefore, clinicians should pay special attention to the increased infection risk when switching pwMS from other disease-modifying therapies (DMTs) to OCRE.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Article
Immunology
Anna-Friederike Marx, Sandra M. Kallert, Tobias M. Brunner, Jose A. Villegas, Florian Geier, Jonas Fixemer, Tiago Abreu-Mota, Peter Reuther, Weldy V. Bonilla, Jelizaveta Fadejeva, Mario Kreutzfeldt, Ingrid Wagner, Patricia Aparicio-Domingo, Leo Scarpellino, Melanie Charmoy, Daniel T. Utzschneider, Claudia Hagedorn, Min Lu, Karen Cornille, Karsten Stauffer, Florian Kreppel, Doron Merkler, Dietmar Zehn, Werner Held, Sanjiv A. Luther, Max Loehning, Daniel D. Pinschewer
Summary: This study shows that T cell factor 1 (Tcf-1) expressing CD8+ T cells, known as stem-like CD8+ T cells (CD8+SL), play a crucial role in immune defense against chronic viral infection and cancer. It identifies interleukin-33 (IL-33) as a pivotal factor for the expansion and functioning of CD8+SL and virus control.
Article
Immunology
Diego von Werdt, Bilgi Gungor, Juliana Barreto de Albuquerque, Thomas Gruber, Daniel Zysset, Cheong K. C. Kwong Chung, Antonia Correa-Ferreira, Regina Berchtold, Nicolas Page, Mirjam Schenk, John H. Kehrl, Doron Merkler, Beat A. Imhof, Jens V. Stein, Jun Abe, Gleb Turchinovich, Daniela Finke, Adrian C. Hayday, Nadia Corazza, Christoph Mueller
Summary: Members of the Regulator of G-protein signaling (Rgs) family regulate G protein signaling by increasing the GTPase activity of G alpha protein subunits. Rgs1, a member of the Rgs family, preferentially deactivates G alpha q and G alpha i subunits, attenuating chemokine receptor-mediated immune cell trafficking. Its impact on tissue-resident T cells and immunosurveillance in barrier tissues is not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Yi-Heng Tai, Daniel Engels, Giuseppe Locatelli, Ioanna Emmanouilidis, Caroline Fecher, Delphine Theodorou, Stephan A. Mueller, Simon Licht-Mayer, Mario Kreutzfeldt, Ingrid Wagner, Natalia Prudente de Mello, Sofia-Natsouko Gkotzamani, Laura Trovo, Arek Kendirli, Almir Aljovic, Michael O. Breckwoldt, Ronald Naumann, Florence M. Bareyre, Fabiana Perocchi, Don Mahad, Doron Merkler, Stefan F. Lichtenthaler, Martin Kerschensteiner, Thomas Misgeld
Summary: In this study, the authors investigate the metabolic and bioenergetic responses in axonal compartments during multiple sclerosis (MS). They demonstrate that upregulating the tricarboxylic acid cycle can protect against energy deprivation induced by neuroinflammation. The researchers use cell-type-specific mitochondrial proteomics and in vivo biosensor imaging to analyze how inflammation alters the molecular composition and function of neuronal mitochondria, finding that neuroinflammatory lesions lead to widespread axonal ATP deficiency and impaired electron transport chain function.
Article
Genetics & Heredity
Danielle Shlesinger, Kai-Lin Hong, Ghazal Shammas, Nicolas Page, Ioana Sandu, Andreas Agrafiotis, Victor Kreiner, Nicolas Fonta, Ilena Vincenti, Ingrid Wagner, Margot Piccinno, Alexandre Mariotte, Bogna Klimek, Raphael Dizerens, Marcos Manero-Carranza, Raphael Kuhn, Roy Ehling, Lester Frei, Keywan Khodaverdi, Camilla Panetti, Nicole Joller, Annette Oxenius, Doron Merkler, Sai T. Reddy, Alexander Yermanos
Summary: This study utilized single-cell sequencing to obtain transcriptome and immune repertoire information related to immune responses. The researchers found correlations between cell phenotypes and factors such as clonal expansion, gene usage, and clonal convergence.
GENES AND IMMUNITY
(2022)
Article
Multidisciplinary Sciences
Laure Garnier, Robert Pick, Julien Montorfani, Mengzhu Sun, Dale Brighouse, Nicolas Liaudet, Thomas Kammertoens, Thomas Blankenstein, Nicolas Page, Jeremiah Bernier-Latamani, Ngoc Lan Tran, Tatiana Petrova, Doron Merkler, Christoph Scheiermann, Stephanie Hugues
Summary: A study found that cytotoxic T cells can reduce lymphatic flow and lymph node metastasis by affecting the tumor lymphatic vessel system. This is achieved through the induction of apoptosis in tumor-associated lymphatic endothelial cells (LECs) by T cells, which is triggered by the release of tumor antigens from dying tumor cells and cross-presentation by LECs.