Article
Multidisciplinary Sciences
Marissa Y. Chou, Dan Liu, Jinping An, Ying Xu, Jason G. Cyster
Summary: B cells that bind soluble autoantigens receive chronic signaling via the B cell receptor (signal-1) in the absence of strong costimulatory signals (signal-2), and this leads to their elimination in peripheral tissues. The factors determining the extent of soluble autoantigen-binding B cell elimination are not fully understood. We found that cathepsin B (Ctsb) promotes the elimination of B cells chronically exposed to signal-1. Ctsb acts extracellularly to reduce soluble autoantigen-binding B cell survival and its actions restrain CD40L-dependent pro-survival effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Gastroenterology & Hepatology
Chao Zhang, Jiesheng Li, Yongqian Cheng, Fanping Meng, Jin-Wen Song, Xing Fan, Hongtao Fan, Jing Li, Yu-Long Fu, Ming-Ju Zhou, Wei Hu, Si-Yu Wang, Yuan-Jie Fu, Ji-Yuan Zhang, Ruo-Nan Xu, Ming Shi, Xueda Hu, Zemin Zhang, Xianwen Ren, Fu-Sheng Wang
Summary: In this study, the comprehensive immune responses in different phases of HBV infection were analyzed using single-cell RNA sequencing. The results showed that both immune active and acute recovery phases were characterized by high levels of exhausted CD8+ T cells in the liver. Significant cell-cell interactions were observed between these exhausted T cells and regulatory CD4+ T cells, as well as between T cells and macrophages. Specific subsets of CD8+ T cells were expanded during the acute recovery phase, providing a potential marker for viral resolution. This study provides important insights into the immunopathogenesis of HBV and the development of effective therapeutic strategies.
Review
Immunology
Andrew Getahun
Summary: This review article focuses on the B cell-intrinsic mechanisms that prevent the activation of autoreactive B cells in the periphery. It discusses the establishment of inhibitory signaling circuits, specifically the Lyn-SHIP-1-SHP-1 axis, and how disruptions of these circuits can contribute to the development of autoimmunity.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Pharmacology & Pharmacy
Kannan Harithpriya, Ravichandran Jayasuriya, Trishla Adhikari, Awantika Rai, Kunka Mohanram Ramkumar
Summary: Transcription factors play crucial roles in regulating gene expression and development of pancreatic B-cells. Hyperglycemia can reduce the expression and/or activities of these transcription factors, leading to loss of B-cell function. Activating transcription factors using small molecules has shown promising results in regenerating and maintaining B-cell function and survival. This review discusses the various transcription factors involved in pancreatic B-cell development and the regulation of their activities in normal and pathological states, as well as the potential pharmacological effects of natural and synthetic compounds on these transcription factors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Nasren Eiza, Adi D. Sabag, Ofra Kessler, Gera Neufeld, Zahava Vadasz
Summary: CD72 serves as a ligand and signal transducing receptor for sema3A, independent of neuropilin-1 (NRP-1), in B cells. Sema3A binding to CD72 on B cells inhibits the phosphorylation of STAT-4 and HDAC-1 and induces the phosphorylation of p38-MAPK and PKC-theta. The sema3A-CD72 axis is a crucial regulatory pathway in the pathogenesis of SLE.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Biology
Elise DeRoo, Ting Zhou, Huan Yang, Amelia Stranz, Peter Henke, Bo Liu
Summary: Through single-cell RNA sequencing, this study identified transcriptomic changes in the vein wall during acute venous thrombosis, including an inflammatory response, hypoxia, and reduced myogenesis. Analysis at the individual cell level revealed increased inflammation and reduced extracellular matrix production in smooth muscle cells and fibroblasts, as well as a phenotypic shift in smooth muscle cell populations. These findings provide new insights into early pathological events that contribute to thrombus formation and adverse venous remodeling.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Alexander Stewart, Joseph Chi-Fung Ng, Gillian Wallis, Vasiliki Tsioligka, Franca Fraternali, Deborah K. Dunn-Walters
Summary: The separation of B cells into different subsets has provided insights into their diverse functions in immune responses. Advances in single-cell techniques have enabled a deeper understanding of B cell characteristics and functions, though challenges remain. This study offers a reference single-cell dataset for better classification of functional B cell subsets in peripheral blood, highlighting the complexity and diversity of B cell populations.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Takeshi Tsubata
Summary: Antibody production to non-protein antigens involves T cell-independent mechanisms, while inhibitory B cell co-receptors suppress B cell response to non-protein self-antigens.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Hsuan Su, Kazuhiro Imai, Wei Jia, Zhiguo Li, Rachel A. DiCioccio, Jonathan S. Serody, Jonathan C. Poe, Benny J. Chen, Phuong L. Doan, Stefanie Sarantopoulos
Summary: De novo immune responses to myeloid and other blood-borne tumors are limited, but vaccination with RNA viral particle vectors can break B-cell tolerance and enable production of anti-tumor antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Thiago Alves da Costa, Jacob N. Peterson, Julie Lang, Jeremy Shulman, Xiayuan Liang, Brian M. Freed, Susan A. Boackle, Pilar Lauzurica, Raul M. Torres, Roberta Pelanda
Summary: The study using a human immune system mouse model revealed a distinctive phenotype of human autoreactive immature B cells and their presence in human bone marrow samples. Additionally, alterations in marker expression were observed in mice engrafted with human immune systems genetically predisposed to autoimmunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Riem Gawish, Barbara Maier, Georg Obermayer, Martin L. Watzenboeck, Anna-Dorothea Gorki, Federica Quattrone, Asma Farhat, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Arman Alimohammadi, Ildiko Mesteri, Felicitas Oberndorfer, Fiona Oakley, John Brain, Louis Boon, Irene Lang, Christoph J. Binder, Sylvia Knapp
Summary: Sepsis can lead to multiorgan failure and therapeutic options are limited. This study establishes a mouse model of long-lasting disease tolerance during severe sepsis and highlights the role of neutrophils and B cells in tissue integrity.
Article
Multidisciplinary Sciences
Ying Wang, Jun Liu, Chizuru Akatsu, Runyun Zhang, Hai Zhang, Han Zhu, Kangwei Liu, Han-Ying Zhu, Qing Min, Xin Meng, Chaoqun Cui, Yue Tang, Meiping Yu, Yaxuan Li, Xiaoqian Feng, Hao Wei, Zichao Wen, Sihan Ji, Martin G. Weigert, Takeshi Tsubata, Ji-Yang Wang
Summary: BCR stimulation induces the upregulation of LAPTM5 expression, which triggers apoptosis of immature B cells through two pathways. LAPTM5 mediates BCR internalization and degradation of WWP2, leading to PTEN accumulation, AKT suppression, increased FOXO1 expression, and upregulation of cell cycle inhibitor p27Kip1 and proapoptotic molecule BIM, ultimately contributing to immature B cell apoptosis and B cell tolerance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Suheeta Roy, Maroun Bou Sleiman, Pooja Jha, Jesse F. Ingels, Casey J. Chapman, Melinda S. McCarty, Jesse D. Ziebarth, Michael Hook, Anna Sun, Wenyuan Zhao, Jinsong Huang, Sarah M. Neuner, Lynda A. Wilmott, Thomas M. Shapaker, Arthur G. Centeno, David G. Ashbrook, Megan K. Mulligan, Catherine C. Kaczorowski, Liza Makowski, Yan Cui, Robert W. Read, Richard A. Miller, Khyobeni Mozhui, Evan G. Williams, Saunak Sen, Lu Lu, Johan Auwerx, Robert W. Williams
Summary: Through experiments on female mice, this study found that a high-fat diet can significantly shorten lifespan. Initial body weight and weight gain are important factors affecting longevity, while the response to a high-fat diet is modulated by gene-environment interactions. Classic serum metabolites may not be strong predictors of longevity.
Article
Immunology
Yiying Yang, Muyuan Li, Yaxi Zhu, Ke Liu, Meidong Liu, Yanjuan Liu, Ganqian Zhu, Hui Luo, Xiaoxia Zuo, Huali Zhang, Muyao Guo
Summary: The aim of this study was to elucidate the role of enhancer of zeste homolog 2 (EZH2) in the breakdown of B cell immune tolerance and production of autoantibodies in systemic lupus erythematosus (SLE), and to explore the therapeutic effects of EZH2 inhibition on lupus. EZH2 expression was elevated in diverse B-cell subsets in both SLE patients and pristane-induced lupus mice. The EZH2 inhibitor attenuated lupus-like symptoms and dampened autoantibody production in pristane-induced lupus mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Paul W. Buehler, Delaney Swindle, David Pak, Scott K. Ferguson, Susan M. Majka, Vijaya Karoor, Radu Moldovan, Chantal Sintas, Jennifer Black, Thomas Gentinetta, Raphael M. Buzzi, Florence Vallelian, Andreas Wassmer, Monika Edler, Joseph Bain, Daniel Schu, Kathryn Hassell, Rachelle Nuss, Dominik J. Schaer, David C. Irwin
Summary: Hemopexin (Hpx) serves as a crucial defense protein against heme stress in sickle cell disease (SCD) patients, with potential therapeutic benefits in improving cardiopulmonary function and exercise tolerance. Regular administrations of Hpx were found to dose-dependently reduce heme exposure and pulmonary hypertension, while also improving cardiac function and reducing fibrosis and oxidative damage in the lungs and heart. Observations in a murine SCD model support the translational potential of Hpx replacement therapy in SCD patients.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Letter
Rheumatology
Vivian E. Saper, Guangbo Chen, R. Paul Guillerman, Purvesh Khatri, Randy Q. Cron, Elizabeth D. Mellins
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Vivian E. Saper, Michael J. Ombrello, Adriana H. Tremoulet, Gonzalo Montero-Martin, Sampath Prahalad, Scott Canna, Chisato Shimizu, Gail Deutsch, Serena Y. Tan, Elaine F. Remmers, Dimitri Monos, Timothy Hahn, Omkar K. Phadke, Elaine Cassidy, Ian Ferguson, Vamsee Mallajosyula, Jianpeng Xu, Jaime S. Rosa Duque, Gilbert T. Chua, Debopam Ghosh, Ann Marie Szymanski, Danielle Rubin, Jane C. Burns, Lu Tian, Marcelo A. Fernandez-Vina, Elizabeth D. Mellins, Jill A. Hollenbach
Summary: Drug reaction with eosinophilia and systemic symptoms (DRESS) can occur in Still's disease patients treated with IL-1/IL-6 inhibitors, with features such as eosinophilia, liver enzyme elevation, and persistent rash. HLA-DRB1*15 haplotypes are significantly enriched in Still's disease with DRESS. Pre-prescription HLA typing and vigilance for serious reactions to these drugs are recommended.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Biochemical Research Methods
Niclas Olsson, Wei Jiang, Lital N. Adler, Elizabeth D. Mellins, Joshua E. Elias
Summary: This study investigates the effects of DO:DM ratios on peptide presentation by creating a panel of HLA-DR4-expressing APC lines and analyzing over 10,000 unique DR4-presented peptides. The findings provide insights into the characteristics that influence peptide presentation and have implications for HLA-II prediction algorithms and research strategies.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Cell Biology
Saborni Chakraborty, Joseph C. Gonzalez, Benjamin L. Sievers, Vamsee Mallajosyula, Srijoni Chakraborty, Megha Dubey, Usama Ashraf, Bowie Yik-Ling Cheng, Nimish Kathale, Kim Quyen Thi Tran, Courtney Scallan, Aanika Sinnott, Arianna Cassidy, Steven T. Chen, Terri Gelbart, Fei Gao, Yarden Golan, Xuhuai Ji, Seunghee Kim-Schulze, Mary Prahl, Stephanie L. Gaw, Sacha Gnjatic, Thomas U. Marron, Miriam Merad, Prabhu S. Arunachalam, Scott D. Boyd, Mark M. Davis, Marisa Holubar, Chaitan Khosla, Holden T. Maecker, Yvonne Maldonado, Elizabeth D. Mellins, Kari C. Nadeau, Bali Pulendran, Upinder Singh, Aruna Subramanian, Paul J. Utz, Robert Sherwood, Sheng Zhang, Prasanna Jagannathan, Gene S. Tan, Taia T. Wang
Summary: A damaging inflammatory response in severe COVID-19 is associated with early non-neutralizing, afucosylated IgG antibodies specific to SARS-CoV-2. Human IgG-Fc-gamma receptor interactions regulate inflammation in the lung, and antibodies elicited by mRNA SARS-CoV-2 vaccines have reduced inflammatory potential.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Debopam Ghosh, Tho D. Pham, Padma P. Nanaware, Deepanwita Sengupta, Lital N. Adler, Caiyun G. Li, Xiao He, Mary E. O'Mara, Aaron B. Kantor, Khoa D. Nguyen, Yang Yang, Laurence C. Eisenlohr, Peter E. Jensen, Leonore A. Herzenberg, Lawrence J. Stern, Scott D. Boyd, Eliver E. B. Ghosn, Elizabeth D. Mellins
Summary: The absence of H2-M protein affects the survival and immunoglobulin selection of B-1 cells, and also alters the specificity of the B-1 cell clonal repertoire.
Article
Allergy
Hesam Movassagh, Mary Prunicki, Abhinav Kaushik, Xiaoying Zhou, Diane Dunham, Eric M. M. Smith, Ziyuan He, German R. Aleman R. Muench, Minyi Shi, Annika K. K. Weimer, Shu Cao, Sandra Andorf, Amir Feizi, Michael P. P. Snyder, Pejman Soroosh, Elizabeth D. D. Mellins, Kari C. C. Nadeau
Summary: This study found that exposure to fine particulate matter (PM2.5) leads to specific alterations in monocytes, especially in children with asthma. Further mechanistic research revealed that fine particulate matter induces innate trained immunity in circulating monocytes, resulting in an enhanced inflammatory response. These findings suggest that the alterations of monocytes may serve as an immune signature for pediatric asthma, and pollution-induced trained immunity could be a potential therapeutic target for asthmatic children.
Article
Developmental Biology
Agnieszka Kalinowski, Lu Tian, Reenal Pattni, Hanna Ollila, Maroof Khan, Cindy Manko, Melissa Silverman, Meiqian Ma, Laurie Columbo, Bahare Farhadian, Susan Swedo, Tanya Murphy, Mats Johnson, Elisabeth Fernell, Christopher Gillberg, Margo Thienemann, Elizabeth D. Mellins, Douglas F. Levinson, Alexander E. Urban, Jennifer Frankovich
Summary: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a sudden-onset neuropsychiatric disorder with an increased prevalence of co-morbid autoimmune illness, particularly arthritis. PANS patients with low C4B copy number are at higher risk for subsequent Juvenile Idiopathic Arthritis (JIA) diagnosis. There is a possible association between low C4B and PANS age of onset, suggesting a potential role of C4B in different types of arthritis.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Developmental Biology
Allison Vreeland, Denise Calaprice, Noga Or-Geva, Richard E. Frye, Dritan Agalliu, Herbert M. Lachman, Christopher Pittenger, Stefano Pallanti, Kyle Williams, Meiqian Ma, Margo Thienemann, Antonella Gagliano, Elizabeth Mellins, Jennifer Frankovich
Summary: Post-infectious neuroinflammation is implicated in acute onset obsessive-compulsive disorder. This review article outlines the evidence supporting the role of neuroinflammation in these disorders, including animal models, imaging studies, and research on sleep and metabolites. The authors encourage interdisciplinary collaboration to further research on clinical syndromes with neuropsychiatric manifestations.
DEVELOPMENTAL NEUROSCIENCE
(2023)
Article
Rheumatology
Kunjan Khanna, Hui Yan, Muneshwar Mehra, Nidhi Rohatgi, Gabriel Mbalaviele, Elizabeth D. Mellins, Roberta Faccio
Summary: This study reveals the regulatory mechanism of NLRP3 inflammasome in systemic juvenile idiopathic arthritis (sJIA). The down-regulation of TMEM178 levels is associated with disease activity and may serve as a marker for identifying patients who would benefit from inflammasome targeting.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Engineering, Biomedical
Fuqiang Ren, Feifei Wang, Ani Baghdasaryan, Ying Li, Haoran Liu, Rusiou Hsu, Chuchu Wang, Jiachen Li, Yeteng Zhong, Felix Salazar, Chun Xu, Yingying Jiang, Zhuoran Ma, Guanzhou Zhu, Xiang Zhao, Kerry Kaili Wong, Richard Willis, K. Christopher Garcia, Anna Wu, Elizabeth Mellins, Hongjie Dai
Summary: This study reports a cancer vaccine that can track and image immune cells non-invasively in vivo, providing insights into the immune responses induced by vaccination. The vaccine rapidly migrates to lymph nodes through lymphatic vessels and eradicates pre-existing tumors with two doses. The use of nanoparticle-based vaccines and imaging probes emitting infrared light has important implications for the design and optimization of immunotherapies.
NATURE BIOMEDICAL ENGINEERING
(2023)
Editorial Material
Health Care Sciences & Services
Jennifer Frankovich, Heer Nanda, Elizabeth D. D. Mellins, Harumi Jyonouchi, Richard G. G. Boles, Stephen J. J. Walker, John Gaitanis, Richard E. E. Frye
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Cell Biology
Justine Maller, Terry Morgan, Mayu Morita, Frank McCarthy, Yunshin Jung, Katrin J. Svensson, Joshua E. Elias, Claudia Macaubas, Elizabeth Mellins
Summary: The study suggests that intercellular communication mediated by extracellular vesicles plays an important role in the pathogenesis of systemic juvenile idiopathic arthritis. The number and cellular sources of extracellular vesicles differ between the active and inactive states of the disease and healthy controls.
JOURNAL OF LEUKOCYTE BIOLOGY
(2023)
Meeting Abstract
Rheumatology
Mariana Correia Marques, Danielle Rubin, Emily Shuldiner, Elizabeth Schmitz, Elizabeth Baskin, Andrew Patt, Alexei Grom, Dirk Foell, Marco Gattorno, John Bohnsack, Rae Yeung, Sampath Prahalad, Elizabeth Mellins, Jordi Anton, Dirk Foell, Marco Gattorno, John Bohnsack, Rae Yeung, Sampath Prahalad, Elizabeth Mellins, Jordi Anton, Claudio Len, Sheila Oliveira, Patricia Woo, Seza Ozen, Michael Ombrello
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Hiroto Nakano, Emily Shuldiner, Anne Hinks, Marc Sudman, Elaine Remmers, Colleen Satorius, Elizabeth Schmitz, Victoria Arthur, Patricia Woo, Alexei Grom, Dirk Foell, John Bohnsack, Marco Gattorno, Seza Ozen, Sampath Prahalad, Rae Yeung, Elizabeth Mellins, Sheila Oliveira, Jordi Anton, Claudio Len, Carol Lake, Ly-Lan Bergeron, Michelle Millwood, Estefania de los Santos, Mariana Correia Marques, Carl Langefeld, Susan Thompson, Wendy Thomson, Michael Ombrello
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Immunology
Shamma Rahman, Achia Khatun, Fabian Gaertner, Claudia Macaubas, Nytzia Licona, Laurie Columbo, Bahare Farhadian, Theresa Willett, Margo Thienemann, Jennifer Frankovich, Elizabeth Mellins
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)