Article
Biochemistry & Molecular Biology
Emanuela Talamonti, Anders Jacobsson, Valerio Chiurchiu
Summary: Omega-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), play important roles in various biological processes and have numerous health benefits. Deficiency in Elovl2, a key enzyme involved in DHA synthesis, leads to decreased DHA levels, increased brain inflammation, and heightened pro-inflammatory responses in T lymphocytes. Additionally, DHA deficiency affects the interaction between dendritic cells (DC) and T cells. Therefore, DHA plays a crucial role in regulating adaptive immunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Denitsa Meteva, Ramona Vinci, Claudio Seppelt, Youssef S. Abdelwahed, Daniela Pedicino, Gregor Nelles, Carsten Skurk, Arash Haghikia, Ursula Rauch-Kroehnert, Teresa Gerhardt, Elisabeth Straessler, Yingjie Zhao, Felix Golla, Michael Joner, Himanshu Rai, Adelheid Kratzer, Hector Giral Arnal, Giovanna Liuzzo, Jens Klotsche, Filippo Crea, Ulf Landmesser, David M. Leistner, Nicolle Kraenkel
Summary: This study identified distinct Toll-like receptor 2 (TLR2)-mediated neutrophil activation in patients with acute coronary syndrome (ACS) and an intact fibrous cap (IFC-ACS). The activation was triggered by elevated levels of soluble hyaluronic acid and resulted in the release of active matrix metalloproteinase 9 (MMP9), promoting endothelial cell loss-triggered thrombosis.
EUROPEAN HEART JOURNAL
(2023)
Article
Medicine, Research & Experimental
Luciana R. Muniz-Bongers, Christopher B. McClain, Mansi Saxena, Gerold Bongers, Miriam Merad, Nina Bhardwaj
Summary: The study revealed that MMP2 plays a promoting role in melanoma tumor growth by reducing cytolytic cells and increasing M2 macrophages. On the other hand, knockdown of MMP2 slows tumor growth and enhances T cell proliferation and NK cell recruitment. These effects of MMP2 are mediated through dysfunctional DC-T cell cross-talk.
Article
Multidisciplinary Sciences
Xuezhi Cao, Yong Liang, Zhenxiang Hu, Huiyu Li, Jiaming Yang, Eric J. Hsu, Jiankun Zhu, Jin Zhou, Yang-Xin Fu
Summary: The study introduces a novel masked IFN-I prodrug activated by tumor-associated proteases, which enhances anti-tumor immune response with reduced toxicity and improved tumor targeting. This engineered prodrug shows prolonged serum half-life, improved tumor-targeting effect, enhanced DC cross-priming, increased CD8(+) infiltration and effector function in the tumor microenvironment, as well as improved checkpoint blockade and radiation efficacy for tumors. Overall, this effective tumor-activating IFN has promising long-term pharmacokinetics with minimal toxicity.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Giuseppe Cosentino, Vincenzo Di Stefano, Rosalia Lo Presti, Maria Montana, Massimiliano Todisco, Matteo Gastaldi, Andrea Cortese, Enrico Alfonsi, Cristina Tassorelli, Brigida Fierro, Gregorio Caimi, Filippo Brighina
Summary: This study found that the plasmatic levels of MMPs and TIMPs were significantly altered in patients with CIDP, with higher concentrations of MMP-9, downregulation of TIMP-1, and lower concentration of MMP-2. These new biomarkers may have potential usefulness in the clinical setting and further studies are needed to confirm their utility.
NEUROLOGICAL SCIENCES
(2021)
Article
Immunology
Wei Zhang, Eun-Koung An, Juyoung Hwang, Jun-O Jin
Summary: The study found that LPS can directly stimulate pDCs via the TLR4/MD2 pathway and promote the activation of pDCs and cDCs. cDCs may contribute to the enhancement of IFN-alpha production in pDCs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rukmini Mukherjee, Anshu Bhattacharya, Denisa Bojkova, Ahmad Reza Mehdipour, Donghyuk Shin, Khadija Shahed Khan, Hayley Hei-Yin Cheung, Kam-Bo Wong, Wai-Lung Ng, Jindrich Cinatl, Paul P. Geurink, Gerbrand J. van der Heden van Noort, Krishnaraj Rajalingam, Sandra Ciesek, Gerhard Hummer, Ivan Dikic
Summary: Famotidine has no effect on viral replication but can modulate specific signaling pathways, reducing TLR3-dependent signaling processes and subsequent activation of IRF3 and the NF-kappa B pathway, leading to control of antiviral and inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Infectious Diseases
Meng-Rui Lee, Yen-Lin Chen, Chang-Wei Wu, Lun-Che Chen, Lih-Yu Chang, Jung-Yueh Chen, Yu-Tsung Huang, Jann-Yuan Wang, Jin-Yuan Shih, Chong-Jen Yu
Summary: This study found that single nucleotide polymorphisms (SNPs) in Toll-like receptor 1 (TLR1), Toll-like receptor 2 (TLR2), and matrix metalloproteinase 8 (MMP8) were associated with the risk of tuberculosis (TB) infection and disease. Haplotypes and a polygenic risk score (PRS) could be used to predict TB disease status.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Pardis Mohammadzadeh, Mina Roueinfar, Gregory C. Amberg
Summary: This study reveals a novel role for AXL as a modulator of GnRH receptor signaling. Gas6 enhances GnRH-dependent ERK phosphorylation and Egr-1 transcript abundance, and promotes LH beta production and pro-MMP9 protein generation, as well as cell migration.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Djalma S. Lima-Junior, Siddharth R. Krishnamurthy, Nicolas Bouladoux, Nicholas Collins, Seong-Ji Han, Erin Y. Chen, Michael G. Constantinides, Verena M. Link, Ai Ing Lim, Michel Enamorado, Christophe Cataisson, Louis Gil, Indira Rao, Taylor K. Farley, Galina Koroleva, Jan Attig, Stuart H. Yuspa, Michael A. Fischbach, George Kassiotis, Yasmine Belkaid
Summary: The skin microbiota stimulates the expression of endogenous retroviruses (ERVs), leading to the induction of commensal-specific T cells and immune responses. Inhibition of ERV reverse transcription impairs immunity and tissue repair, while a lipid-enriched diet enhances ERV expression for heightened immune responses and inflammation in response to colonization by commensal microbes.
Article
Biochemistry & Molecular Biology
Ya-Tang Chiang, Yu-Bai Xiao, Shan-hui Hsu, Shu-Wei Chang, Chia-Ching Chou
Summary: Tannic acid (TA) has antibacterial, antioxidant, and anti-inflammatory properties and acts as an adhesive, hemostatic, and crosslinking agent in hydrogels. TA has been reported to inhibit MMP-2/- 9 activities, thereby improving tissue remodeling and wound healing. In this study, atomistic modeling was used to explore the mechanisms and structures of TA binding with MMP-2 and MMP-9, revealing the specific binding regions and molecular interactions involved. Understanding the binding mechanism and dynamics of TA with these MMPs provides crucial knowledge on the effects of TA on MMPs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Immunology
Maarten K. Nijen Twilhaar, Lucas Czentner, Rianne G. Bouma, Katarzyna Olesek, Joanna Grabowska, Aru Zeling Wang, Alsya J. Affandi, Saskia C. Belt, Hakan Kalay, Cornelus F. van Nostrum, Yvette van Kooyk, Gert Storm, Joke M. M. den Haan
Summary: TLR-containing GM3 liposomes are effective vectors to induce DC maturation and T cell priming. Incorporation of PGPC or MDP does not enhance immune responses. These findings provide guidance for the optimal selection of liposomal components to stimulate anti-cancer immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Endocrinology & Metabolism
Marco Di Gioia, Ivan Zanoni
Summary: Endogenous oxidized phospholipids play a key role in sustaining inflammatory responses and can affect the biology and function of phagocytes, leading to the development of chronic inflammatory diseases. Understanding the mechanisms of action of these oxidized lipids is crucial for designing interventions.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Klatka, Agnieszka Polak, Paulina Mertowska, Sebastian Mertowski, Jakub Lyczba, Anna Hymos, Izabela Korona-Glowniak, Ewelina Grywalska
Summary: Chronic lymphocytic thyroiditis, or HD, is a common thyroid disorder. Research has focused on the role of Toll-like receptors (TLRs), particularly TLR2, in the pathogenesis of HD. This study found a significant increase in TLR2 expression on immune cells and a higher concentration of soluble TLR2 in plasma in HD patients compared to healthy individuals. TLR2 expression also correlated with thyroid function indicators. These findings suggest that TLR2 may be involved in the immunopathogenesis of HD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sang Yeol Lee
Summary: Matrix metalloproteinases (MMPs) play crucial roles in cancer metastasis and chronic inflammatory diseases, while ginsenosides have therapeutic potentials. Ginsenosides exhibit anti-metastatic and anti-inflammatory activities by suppressing MMPs through regulation of various signaling pathways.
Article
Cell Biology
Alexandra C. Walls, Laura A. VanBlargan, Kai Wu, Angela Choi, Mary Jane Navarro, Diana Lee, Laura Avena, Daniela Montes Berrueta, Minh N. Pham, Sayda Elbashir, John C. Kraft, Marcos C. Miranda, Elizabeth Kepl, Max Johnson, Alyssa Blackstone, Kaitlin Sprouse, Brooke Fiala, Megan A. O'Connor, Natalie Brunette, Prabhu S. Arunachalam, Lisa Shirreff, Kenneth Rogers, Lauren Carter, Deborah H. Fuller, Francois Villinger, Bali Pulendran, Michael S. Diamond, Darin K. Edwards, Neil P. King, David Veesler
Summary: The use of BALB/c mice as an animal model to study neutralizing antibody responses against SARS-CoV-2 variants of concern (VOCs) may not accurately reflect the breadth and potency of responses observed in non-human primates or humans vaccinated with various vaccine platforms.
Article
Immunology
Slim Fourati, Lewis E. Tomalin, Matthew P. Mule, Daniel G. Chawla, Bram Gerritsen, Dmitry Rychkov, Evan Henrich, Helen E. R. Miller, Thomas Hagan, Joann Diray-Arce, Patrick Dunn, Ofer Levy, Raphael Gottardo, Minnie M. Sarwal, John S. Tsang, Mayte Suarez-Farinas, Bali Pulendran, Steven H. Kleinstein, Rafick-Pierre Sekaly
Summary: Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. This study identified a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. The results suggest that the transcriptional state of the immune system can determine responsiveness to vaccination.
Article
Immunology
Wei Luo, Julia Z. Z. Adamska, Chunfeng Li, Rohit Verma, Qing Liu, Thomas Hagan, Florian Wimmers, Shakti Gupta, Yupeng Feng, Wenxia Jiang, Jiehao Zhou, Erika Valore, Yanli Wang, Meera Trisal, Shankar Subramaniam, Timothy F. Osborne, Bali Pulendran
Summary: Our previous study showed that the sterol regulatory binding protein (SREBP) pathway is associated with humoral immune response. We generated mice with specific deletion of SCAP, an essential regulator of SREBP signaling, in B cells or CD11c(+) antigen-presenting cells (APCs). Deletion of SCAP in CD11c(+) APCs had no impact on immune responses, whereas SREBP signaling in B cells was crucial for antibody responses and the development of immune cells. These studies reveal the regulatory role of sterol metabolism in humoral immunity.
Correction
Immunology
Amy C. Palin, Galit Alter, Shane Crotty, Ali H. Ellebedy, M. Chelsea Lane, F. Eun-Hyung Lee, Michela Locci, Angela Malaspina, Conrad Mallia, M. Juliana McElrath, Bali Pulendran, Anjali Singh, M. Patricia D'Souza
Article
Chemistry, Physical
Qian Yin, Wei Luo, Vamsee Mallajosyula, Yang Bo, Jing Guo, Jinghang Xie, Meng Sun, Rohit Verma, Chunfeng Li, Christian M. M. Constantz, Lisa E. E. Wagar, Jing Li, Elsa Sola, Neha Gupta, Chunlin Wang, Oliver Kask, Xin Chen, Xue Yuan, Nicholas C. C. Wu, Jianghong Rao, Yueh-hsiu Chien, Jianjun Cheng, Bali Pulendran, Mark M. M. Davis
Summary: This study uses a nanoparticle-based adjuvant to enhance immune responses against multiple variants of influenza and SARS-CoV-2, generating cross-reactive antibodies for both dominant and subdominant epitopes. The adjuvant shows promising implications for developing broadly protective vaccines, as it improves lymph node targeting, activates immune cells, and leads to broad immune responses. The adjuvanted vaccines successfully protect mice against viral challenges of different strains and enhance antibody responses to SARS-CoV-2 subunit vaccines against multiple viral variants.
Article
Cell Biology
Julia Z. Adamska, Rohit Verma, Shakti Gupta, Thomas Hagan, Florian Wimmers, Katharine Floyd, Qin Li, Erika V. Valore, Yanli Wang, Meera Trisal, Jose G. Vilches-Moure, Shankar Subramaniam, Carl R. Walkley, Mehul S. Suthar, Jin Billy Li, Bali Pulendran
Summary: Deletion of ADAR1 in CD11c+ APCs leads to changes in immune response, including enrichment of inflammatory cells, increased activated tissue resident memory T cells, and broad changes in antiviral transcriptional signature. These changes can be partially reversed by blocking IFNAR1 signaling and promote early resistance against SARS-CoV-2 infection.
Article
Multidisciplinary Sciences
Jennifer Cable, Barney S. Graham, Richard A. Koup, Robert A. Seder, Katalin Kariko, Norbert Pardi, Dan H. Barouch, Bhawna Sharma, Susanne Rauch, Raffael Nachbagauer, Mattias N. E. Forsell, Michael Schotsaert, Ali H. Ellebedy, Karin Lore, Darrell J. Irvine, Emily Pilkington, Siri Tahtinen, Elizabeth A. Thompson, Yanis Feraoun, Neil P. King, Kevin Saunders, Galit Alter, Syed M. Moin, Kwinten Sliepen, Gunilla B. Karlsson Hedestam, Hedda Wardemann, Bali Pulendran, Nicole A. Doria-Rose, Wan-Ting He, Jennifer A. Juno, Sila Ataca, Adam K. Wheatley, Jason S. McLellan, Laura M. Walker, Julia Lederhofer, Lisa C. Lindesmith, Holger Wille, Peter J. Hotez, Linda-Gail Bekker
Summary: The COVID-19 pandemic has highlighted the importance of vaccines in public health and advancements in vaccine technology are vital for preventing infectious diseases. While many diseases still lack effective vaccines, recent developments in fields like immunology and structural biology may lead to breakthroughs in vaccination and enhance preparedness for future pandemics.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Immunology
Fei Gao, Vamsee Mallajoysula, Prabhu S. Arunachalam, Kattria van der Ploeg, Monali Manohar, Katharina Roltgen, Fan Yang, Oliver Wirz, Ramona Hoh, Emily Haraguchi, Ji-Yeun Lee, Richard Willis, Vasanthi Ramachandiran, Jiefu Li, Karan Raj Kathuria, Chunfeng Li, Alexandra S. Lee, Mihir M. Shah, Sayantani B. Sindher, Joseph Gonzalez, John D. Altman, Taia T. Wang, Scott D. Boyd, Bali Pulendran, Prasanna Jagannathan, Kari C. Nadeau, Mark M. Davis
Summary: T cells play a crucial role in the immune response to SARS-CoV-2, but their behavior after infection and vaccination is not well understood. This study examined the T cell responses of subjects receiving the Pfizer/BioNTech BNT162b2 vaccine. Vaccination induced strong spike-specific T cell responses for both CD4+ and CD8+ T cells, with CD4+ responses peaking 1 week after the second dose and CD8+ responses peaking 2 weeks later. These T cell responses were higher than those observed in COVID-19 patients. Additionally, prior SARS-CoV-2 infection was found to decrease CD8+ T cell activation and expansion, suggesting an influence of previous infection on the T cell response to vaccination.
Correction
Multidisciplinary Sciences
Prabhu S. Arunachalam, Madeleine K. D. Scott, Thomas Hagan, Chunfeng Li, Yupeng Feng, Florian Wimmers, Lilit Grigoryan, Meera Trisal, Venkata Viswanadh Edara, Lilin Lai, Sarah Esther Chang, Allan Feng, Shaurya Dhingra, Mihir Shah, Alexandra S. Lee, Sharon Chinthrajah, Sayantani B. Sindher, Vamsee Mallajosyula, Fei Gao, Natalia Sigal, Sangeeta Kowli, Sheena Gupta, Kathryn Pellegrini, Gregory Tharp, Sofia Maysel-Auslender, Sydney Hamilton, Hadj Aoued, Kevin Hrusovsky, Mark Roskey, Steven E. Bosinger, Holden T. Maecker, Scott D. Boyd, Mark M. Davis, Paul J. Utz, Mehul S. Suthar, Purvesh Khatri, Kari C. Nadeau, Bali Pulendran
Article
Multidisciplinary Sciences
Laura Amaya, Lilit Grigoryan, Zhijian Li, Audrey Lee, Paul A. Wender, Bali Pulendran, Howard Y. Chang
Summary: Circular RNAs (circRNAs) are highly stable RNAs that can be engineered to provide durable protein expression. This study shows that circRNA encoding antigenic protein sequences delivered by a charge-altering releasable transporter can serve as both an adjuvant and an immunogen, inducing potent cellular immunity and leading to tumor clearance as a therapeutic vaccine. These results suggest the potential utility of engineered circRNAs for the development of vaccines and therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Yupeng Feng, Meng Yuan, John M. Powers, Mengyun Hu, Jennifer E. Munt, Prabhu S. Arunachalam, Sarah R. Leist, Lorenza Bellusci, JungHyun Kim, Kaitlin R. Sprouse, Lily E. Adams, Sumana Sundaramurthy, Xueyong Zhu, Lisa M. Shirreff, Michael L. Mallory, Trevor D. Scobey, Alberto Moreno, Derek T. O'Hagan, Harry Kleanthous, Francois J. Villinger, David Veesler, Neil P. King, Mehul S. Suthar, Surender Khurana, Ralph S. Baric, Ian A. Wilson, Bali Pulendran
Summary: This study identified highly potent monoclonal antibodies (mAbs) from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines that neutralized multiple sarbecoviruses. The antibodies generated from antigen-specific memory B cells (MBCs) exhibited increasing potency and breadth over a period of 8-15 months after vaccination. Some of the antibodies also showed neutralizing activity against the SARS-CoV-2 BA.1 variant. Crystallography studies revealed the molecular basis of the broad and potent neutralization.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Payton A. -B. Weidenbacher, Mrinmoy Sanyal, Natalia Friedland, Shaogeng Tang, Prabhu S. Arunachalam, Mengyun Hu, Ozan S. Kumru, Mary Kate Morris, Jane Fontenot, Lisa Shirreff, Jonathan Do, Ya-Chen Cheng, Gayathri Vasudevan, Mark B. Feinberg, Francois J. Villinger, Carl Hanson, Sangeeta B. Joshi, David B. Volkin, Bali Pulendran, Peter S. Kim
Summary: While the development of COVID-19 vaccines has been successful, there is a need for a globally available vaccine that provides longer-lasting immunity against current and future variants of concern. One potential vaccine candidate is DCFHP, a protein-nanoparticle vaccine formulated with aluminum hydroxide as the adjuvant. It has shown promising results in eliciting potent and durable neutralizing antibodies in non-human primates against known variants and can be produced in large quantities. DCFHP has the potential to be used as a booster vaccine or as a primary vaccine for pediatric use.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Florian Wimmers, Allison R. Burrell, Yupeng Feng, Hong Zheng, Prabhu S. Arunachalam, Mengyun Hu, Sara Spranger, Lindsay E. Nyhoff, Devyani Joshi, Meera Trisal, Mayanka Awasthi, Lorenza Bellusci, Usama Ashraf, Sangeeta Kowli, Katherine C. Konvinse, Emily Yang, Michael Blanco, Kathryn Pellegrini, Gregory Tharp, Thomas Hagan, R. Sharon Chinthrajah, Tran T. Nguyen, Alba Grifoni, Alessandro Sette, Kari C. Nadeau, David B. Haslam, Steven E. Bosinger, Jens Wrammert, Holden T. Maecker, Paul J. Utz, Taia T. Wang, Surender Khurana, Purvesh Khatri, Mary A. Staat, Bali Pulendran
Summary: This study used a multi-omics approach to investigate immunity to SARS-CoV2 in infants and young children. The results showed that infants mounted a robust mucosal immune response and had long-lasting antibody titers.
Article
Medicine, Research & Experimental
Prabhu S. Arunachalam, Lilin Lai, Hady Samaha, Yupeng Feng, Mengyun Hu, Harold Sai-yin Hui, Bushra Wali, Madison Ellis, Meredith E. Davis-Gardner, Christopher Huerta, Kareem Bechnak, Sarah Bechnak, Matthew Lee, Matthew B. Litvack, Cecilia Losada, Alba Grifoni, Alessandro Sette, Veronika I. Zarnitsyna, Nadine Rouphael, Mehul S. Suthar, Bali Pulendran
Summary: The durability of serum antibody responses only marginally improves after booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Correction
Medicine, General & Internal
Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise A. Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Chris Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David Corry, Farrah Kheradmand, Lauren I. R. Ehrlich, Esther Melamed, Grace A. Mccomsey, Rafick Sekaly, Joann Diray-Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Matthew C. Altman, Patrice M. Becker, Nadine Rouphael