Article
Immunology
Jorge H. Tabares-Guevara, Julio C. Jaramillo, Laura Ospina-Quintero, Christian A. Piedrahita-Ochoa, Natalia Garcia-Valencia, David E. Bautista-Erazo, Erika Caro-Gomez, Camila Covian, Angello Retamal-Diaz, Luisa F. Duarte, Pablo A. Gonzalez, Susan M. Bueno, Claudia A. Riedel, Alexis M. Kalergis, Jose R. Ramirez-Pineda
Summary: The use of natural IL-10-inducing small molecules can potentially address chronic inflammatory diseases by modulating the effector/regulatory balance of the immune system, showcasing a promising immunopharmacological potential.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Maria N. Navarro, Manuel M. Gomez de las Heras, Maria Mittelbrunn
Summary: Immune metabolism is closely related to cellular functions such as energy metabolism and inflammation. The manipulation of NAD(+) availability through pharmacological compounds can have immune-modulatory properties in inflammation, offering opportunities for therapeutic intervention in inflammatory disorders.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alicia Ballester, Adriana Guijarro, Beatriz Bravo, Javier Hernandez, Rodolfo Murillas, Marta Gallego, Sara Ballester
Summary: This study investigated the role of the Hedgehog (Hh) pathway in modulating the immune response. The results showed that Hh pathway activation favored the Th2 phenotype and impaired the establishment of the Th1 phenotype. Additionally, mice with constitutive activation of the Hh pathway showed a milder response to inflammatory challenge and less spinal cord damage. These findings demonstrate the involvement of the Hh/ptch pathway in immune response modulation and highlight the potential of the ptch(+/-) mouse model for studying T-cell-mediated diseases and developing new therapeutic strategies for inflammatory diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Eryn Bugbee, Angela A. Wang, Jennifer L. Gommerman
Summary: The IL-10/IL-10 receptor axis has an important role in reducing neuroinflammation in animal models of Multiple Sclerosis (MS), and increased IL-10 is associated with a positive response to MS disease modifying therapy. Identification of environmental factors impacting the IL-10/IL-10 receptor axis could have therapeutic potential. This review discusses the impact of IL-10 receptor signaling on neuroinflammation, environmental factors and intestinal microbes that affect the IL-10/IL-10 receptor axis, and proposes a hypothetical model for the role of B cells in conveying environmental information to the inflamed central nervous system.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Alba Sanchez-Fernandez, Stephanie Zandee, Jesus Amo-Aparicio, Marc Charabati, Alexandre Prat, Cecilia Garlanda, Elan Z. Eisenmesser, Charles A. Dinarello, Ruben Lopez-Vales
Summary: This study demonstrates that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. Administration of recombinant human IL-37 exerts therapeutic actions in EAE mice, but IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and brain lesions of MS patients.
Article
Chemistry, Analytical
Mao Fukuyama, Suguru Nishinami, Yoko Maruyama, Taiki Ozawa, Shunsuke Tomita, Yumiko Ohhashi, Motohiro Kasuya, Masao Gen, Eri Chatani, Kentaro Shiraki, Akihide Hibara
Summary: This study developed a measurement method for the amyloid droplet nucleation rate based on image analysis, and found that LLPS unexpectedly suppressed amyloid nucleation in the droplets of a prion disease model protein.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhongju Ye, Zhao-Jun Yan, Chenhong Zhang, Jun-Li Hou, Shijing Yue, Lehui Xiao
Summary: Anti-A beta therapy has been the main focus in clinical trials for AD prevention and treatment. This study introduced a new strategy using a charged tubular supramolecule to suppress A beta fibrillation, showing efficient inhibition of A beta(40) fibrillation by CTS-A at a very low inhibitor:peptide molar ratio (1:10) and a reduced cytotoxic effect of A beta peptides post-inhibition or disaggregation. The organized supramolecular structure enhances amyloid fibrillar modulation, offering a new approach for AD treatment using supramolecules.
Article
Immunology
Ashley A. Brate, Alexander W. Boyden, Isaac J. Jensen, Vladimir P. Badovinac, Nitin J. Karandikar
Summary: This study identifies a disease-suppressing subset of CD8 T cells with unique phenotypic properties, including a CXCR3(+) subpopulation and increased degranulation and coproduction of IFN-gamma and IL-10. Understanding the functional characteristics of this regulatory subset provides insights into potential novel immunotherapeutic approaches for MS.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Lihi Radomir, Matthias P. Kramer, Michal Perpinial, Nofar Schottlender, Stav Rabani, Keren David, Anna Wiener, Hadas Lewinsky, Shirly Becker-Herman, Rina Aharoni, Ron Milo, Claudia Mauri, Idit Shachar
Summary: Regulatory B (Breg) cells suppress excessive inflammation primary via the production of interleukin 10 (IL-10). Here the authors show that the function and homeostasis of mouse and human IL-10(+) Breg cells are negatively regulated by the cell surface receptor, SLAMF5, to impact experimental autoimmunity, thereby hinting SLAMF5 as a potential target for immunotherapy.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Anastasia Geladaris, Silke Haeusser-Kinzel, Roxanne Pretzsch, Nitzan Nissimov, Klaus Lehmann-Horn, Darius Haeusler, Martin S. Weber
Summary: B cells contribute to chronic inflammatory conditions, but removal of B cells may enhance the activity of monocytes. B cell-provided interleukin-10 (IL-10) plays a key role in controlling the pro-inflammatory activity of peripheral myeloid cells and microglia. Depleting B cells in a mouse model of multiple sclerosis (MS) accelerates disease severity, while adoptive transfer of IL-10-providing B cells reverses clinical exacerbation.
ACTA NEUROPATHOLOGICA
(2023)
Article
Chemistry, Multidisciplinary
Jinwon Park, Quoc-Viet Le, Yina Wu, Jaiwoo Lee, Yu-Kyoung Oh
Summary: A tolerogenic nanovaccine has been developed and tested on an animal model of multiple sclerosis. The nanovaccine delivers a self-antigen to dendritic cells, blocking the interaction between immune cells and reducing interferon gamma secretion. The results show that the nanovaccine has significant preventive and therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Jin Kyeong Choi, Cheng-Rong Yu, So Jin Bing, Yingyos Jittayasothorn, Mary J. Mattapallil, Minkyung Kang, Seung Bum Park, Hyun-Su Lee, Lijin Dong, Guangpu Shi, Rachel R. Caspi, Charles E. Egwuagu
Summary: Natural regulatory B-1a cells producing IL-27 (i27-Bregs) have been identified in the peritoneal cavity and human umbilical cord blood, accumulating in the CNS during neuroinflammation to confer protection against autoimmune diseases. i27-Breg immunotherapy ameliorated encephalomyelitis and uveitis through up-regulating inhibitory receptors, suppressing immune responses, and converting conventional B cells to secrete IL-10 and/or IL-35.Mutation of irf4 in B cells resulted in increased i27-Bregs with few i35-Bregs, while loss of irf8 led to an abundance of i35-Bregs but impaired generation of i27-Bregs, suggesting the role of IRF8/BATF and IRF4/BATF axis in regulating B cell differentiation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Theresa Greiner, Markus Kipp
Summary: Multiple sclerosis initially presents with a relapsing-remitting disease course, then progresses to a secondary progressive stage. In both stages, peripheral immune cells are triggered by CNS-intrinsic stimuli to invade the brain parenchyma.
Article
Microbiology
Michelle Coleman, Austyn Orvis, Alyssa Brokaw, Anna Furuta, Kavita Sharma, Phoenicia Quach, Avneet Bhullar, Rhea Sanghavi, Shayla Nguyen, Erin Sweeney, Ravin Seepersaud, Blair Armistead, Kristina M. Adams Waldorf, Lakshmi Rajagopal
Summary: Bacterial infections, such as group B streptococcus (GBS) and Streptococcus agalactiae, can lead to adverse pregnancy outcomes. GBS hyaluronidase (HylB) breaks down host hyaluronan and dampens protective TLR2 and TLR4 signaling, promoting GBS dissemination in pregnant women. However, mice lacking TLR2 and TLR4 are able to control GBS infection. IL-10 and IL-10-expressing macrophages play a role in immune suppression and GBS dissemination during pregnancy.
Article
Multidisciplinary Sciences
Hiroaki Matsushita, Atsushi Fukunari, Gento Sameshima, Masamitsu Okada, Fumika Inoue, Mitsuharu Ueda, Yukio Ando
Summary: UV irradiation has been found to reduce amyloid fibril formation, but its effects vary depending on the type of amyloidogenic protein. The amount of aggregates does not differ significantly with or without UV irradiation.
JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES
(2022)
Article
Immunology
Bao Ying Chen, Jessica R. Salas, Alyssa O. Trias, Arely Perez Rodriguez, Jonathan E. Tsang, Miriam Guemes, Thuc M. Le, Zoran Galic, H. Michael Shepard, Lawrence Steinman, David A. Nathanson, Johannes Czernin, Owen N. Witte, Caius G. Radu, Kenneth A. Schultz, Peter M. Clark
Summary: Research on multiple sclerosis and autoimmune diseases has found that targeting deoxycytidine kinase (dCK) can limit the progression of symptoms, and dCK activity is essential for activation-induced proliferation in specific lymphocytes.
Article
Clinical Neurology
Carolyn Goldschmidt, Steven L. Galetta, Robert P. Lisak, Laura J. Balcer, Andrew Hellman, Michael K. Racke, Amy E. Lovett-Racke, Roberto Cruz, Matthew S. Parsons, Neda Sattarnezhad, Lawrence Steinman, Scott S. Zamvil, Elliot M. Frohman, Teresa C. Frohman
Summary: A woman was diagnosed with relapsing-remitting multiple sclerosis (MS) as a teenager and later developed neuromyelitis optica spectrum disorder in her sixties. This case highlights the importance of reconsidering the working diagnosis when faced with evidence of a distinctly different disorder.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
Review
Immunology
Lawrence Steinman, Roberto Patarca, William Haseltine
Summary: Twenty years ago, a tribute was published in this journal to celebrate the 70th anniversary of an animal model known as experimental autoimmune encephalomyelitis (EAE). Recent research has helped explain how Epstein-Barr virus triggers multiple sclerosis through molecular mimicry. These observations bring us back to Rivers' first paper on EAE, published 90 years ago, and show the continued importance of this animal model in understanding disease mechanisms.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Nutrition & Dietetics
Dohyup Kim, Emily E. Witt, Simone Schubert, Elias Sotirchos, Pavan Bhargava, Ellen M. Mowry, Karen Sachs, Biter Bilen, Lawrence Steinman, Avni Awani, Zihuai He, Peter A. Calabresi, Keith Van Haren
Summary: The gene expression profile of vitamin D in the immune system may vary by cell type. Future clinical studies should consider techniques that allow for cell-type resolution.
Article
Multidisciplinary Sciences
Sharon A. Sagan, Zahra Moinfar, Carson E. Moseley, Ravi Dandekar, Collin M. Spencer, Alan S. Verkman, Ole Petter Ottersen, Raymond A. Sobel, John Sidney, Alessandro Sette, Mark S. Anderson, Lawrence Steinman, Michael R. Wilson, Joseph J. Sabatino, Scott S. Zamvil
Summary: This study investigates the role of AQP4-specific Th17 cells in the pathogenesis of neuromyelitis optica (NMO). The research shows that AQP4-specific T cells have a high affinity for binding to MHC II, and their clonal expansion is observed in AQP4-deficient mice. Thymic negative selection alone does not account for the tolerance to AQP4 in wild-type (WT) mice. AQP4-specific Th17 cells can cause paralysis followed by recovery, associated with apoptosis of donor T cells. However, these cells can persist and cause persistent paralysis in mice deficient in both T and B cells or lacking T cells only. In contrast, MOG-specific T cells survive and cause sustained disease in WT mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Aude Chiot, Shanu F. Roemer, Lisa Ryner, Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A. Jimenez, Michael Leviten, Randall Woltjer, Dennis W. Dickson, Lawrence Steinman, Bahareh Ajami
Summary: This study found that alpha 5 integrin is prominently expressed in motor pathways and perivascular zones associated with the blood-brain barrier in ALS patients and mouse models. Treatment with an antibody against alpha 5 integrin improved survival and motor function in the mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Tobias Lanz, William H. Robinson, Peggy P. Ho, Lawrence Steinman
Summary: We propose studying the molecular mechanisms underlying the clonal antibody response in cerebrospinal fluid and exploring therapeutic approaches to block EBV-triggered multiple sclerosis. These include antiviral clinical trials, development of nucleic acid-based vaccines, cellular adoptive therapy, and vaccines to EBV. These topics are not exhaustive, but our medical science community has the tools to tackle EBV-triggered MS and potentially eradicate the disease, as we have done with poliomyelitis.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Meeting Abstract
Clinical Neurology
K. W. Selmaj, L. Steinman, G. Comi, A. Bar-Or, H. P. Hartung, X. Montalban, E. K. Havrdova, J. K. Sheffield, A. Thorpe, J. V. Riolo, A. Krakovich, C. Y. Cheng, L. Kappos, J. A. Cohen, B. A. C. Cree
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Meeting Abstract
Clinical Neurology
Enrique Alvarez, Lawrence Steinman, Hans-Peter Hartung, Edward Fox, Peiqing Qian, Sibyl Wray, Derrick Robertson, Koby Mok, Christopher A. Garner, Bruce Cree
Meeting Abstract
Clinical Neurology
Lawrence Steinman, Edward Fox, Hans-Peter Hartung, Enrique Alvarez, Peiqing Qian, Sibyl Wray, Derrick Robertson, Deren Huang, Krzysztof Selmaj, Daniel Wynn, Jenna Bosco, Koby Mok, Christopher A. Garner, Bruce Cree
Meeting Abstract
Clinical Neurology
K. W. Selmaj, J. A. Cohen, L. Steinman, G. Comi, A. Bar-Or, H. Hartung, X. Montalban, L. Kappos, J. K. Sheffield, A. Krakovich, C. Cheng, J. Riolo, D. Silva, B. A. Cree
MULTIPLE SCLEROSIS JOURNAL
(2023)
Meeting Abstract
Clinical Neurology
B. A. Cree, K. Selmaj, L. Steinman, G. Comi, A. Bar-Or, D. L. Arnold, H. Hartung, X. Montalban, E. K. Havrdova, J. K. Sheffield, C. Cheng, J. V. Riolo, D. Silva, L. Kappos, J. A. Cohen
MULTIPLE SCLEROSIS JOURNAL
(2023)
Meeting Abstract
Clinical Neurology
T. V. Lanz, R. C. Brewer, P. P. Ho, L. Steinman, W. H. Robinson
MULTIPLE SCLEROSIS JOURNAL
(2023)
Meeting Abstract
Clinical Neurology
E. J. Fox, L. Steinman, H. -P. Hartung, E. Alvarez, P. Qian, S. Wray, D. Robertson, D. Huang, K. Selmaj, D. Wynn, J. A. Bosco, L. Lee, B. A. C. Cree
MULTIPLE SCLEROSIS JOURNAL
(2022)
Meeting Abstract
Clinical Neurology
H. -P. Hartung, L. Steinman, A. Bar-Or, J. K. Sheffield, S. Harris, J. V. Riolo, C. -Y. Cheng, D. Silva, B. A. C. Cree
MULTIPLE SCLEROSIS JOURNAL
(2022)