Review
Biochemistry & Molecular Biology
Yasuyuki Tanahashi, Seiichi Komori, Hayato Matsuyama, Takio Kitazawa, Toshihiro Unno
Summary: The article reviews the mechanism of mAChRs in regulating gastrointestinal smooth muscle function and highlights the major signaling events induced by mAChRs. Challenges in studying individual mAChR subtypes and the need for novel strategies such as genetic manipulation are emphasized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Grethe Skovbjerg, Urmas Roostalu, Henrik H. Hansen, Thomas A. Lutz, Christelle Le Foll, Casper G. Salinas, Jacob L. Skytte, Jacob Jelsing, Niels Vrang, Jacob Hecksher-Sorensen
Summary: Amylin plays a key role in regulating energy homeostasis and glycaemic control by stimulating satiation and reducing food reward. The study identifies global brain-wide changes in response to amylin and reveals the importance of RAMP1/3 receptors in mediating this response. Neuronal activation in various brain regions is affected by amylin dosing, indicating its broad impact on neuronal appetite regulation.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Immunology
Yafei Deng, Qinglan Yang, Yao Yang, Yana Li, Hongyan Peng, Shuting Wu, Shuju Zhang, Baige Yao, Shuhui Li, Yuan Gao, Xiaohui Li, Liping Li, Youcai Deng
Summary: The study reveals the critical role of ROR gamma t-expressing cells in the brain, with Tsc1(ROR gamma t) mice displaying spontaneous seizures and death between 4 and 6 weeks of age. Additionally, cortical neuron defects, hippocampal structural abnormalities, and over-activation of neurons and astrogliosis were observed in the brains of these mice.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Yoshinori Ohmura, Naoki Ishimori, Akimichi Saito, Takashi Yokota, Shunpei Horii, Satoshi Tokuhara, Kazuya Iwabuchi, Hiroyuki Tsutsui
Summary: Our study demonstrated that iNKT cells are involved in exacerbating plaque instability by activating inflammatory cells and upregulating MMP-2 in vascular tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Marc Rosenbaum, Theresa Schnalzger, Thomas Engleitner, Christin Weiss, Ritu Mishra, Cora Mibus, Theresa Mitterer, Roland Rad, Juergen Ruland
Summary: The study reveals that MALT1 protease activity controls the upregulation of MYC transcription factor and its target genes in Tregs, influencing mitochondrial function, respiratory capacity, and proliferation. This mechanism is crucial for the maintenance of immune homeostasis in Tregs.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Xueyan Ding, Yajie Chang, Siquan Wang, Dong Yan, Jiakui Yao, Guoqiang Zhu
Summary: The study revealed that GAT-2 deficiency promotes the differentiation of naive T cells into Th1 cells and affects several signaling pathways and metabolic pathways.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Binbin Song, Shigeki Aoki, Cong Liu, Takeshi Susukida, Saki Kuwahara, Kousei Ito
Summary: Based on studies using a transgenic mouse model, it was found that severe abacavir-induced skin hypersensitivity could be induced by depleting PD1 and CD4 T cells, which led to CD8 T cell activation and dendritic cell maturation.
Article
Cell Biology
Karla C. Fischer, Carmel P. Daunt, Cedric S. Tremblay, Sheila Dias, James E. Vince, Anissa M. Jabbour
Summary: The I kappa B kinase complex is crucial for haematopoietic cell development and function, particularly with the deletion of IKK2 leading to various abnormalities such as neutrophilia, severe anaemia, thrombocytosis, and immune inflammation.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Jesse Goyette, David Depoil, Zhengmin Yang, Samuel A. Isaacson, Jun Allard, P. Anton van der Merwe, Katharina Gaus, Michael L. Dustin, Omer Dushek
Summary: Protein-protein binding domains, such as the Src homology 2 (SH2) domains, play a critical role in signaling networks. Tandem SH2 domains can enhance binding affinity and specificity, but there is a trade-off between long-lived binding and rapid signaling reversal. This study shows that phosphatases can accelerate the unbinding rate of tandem SH2 domains, breaking the trade-off and allowing for efficient T cell antigen discrimination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Ilaria Morella, Veronika Pohorala, Claudia Calpe-Lopez, Riccardo Brambilla, Rainer Spanagel, Rick E. Bernardi
Summary: This study examined the role of the Ras-ERK signaling pathway in nicotine-related reward behaviors and found that RasGRF2 regulates the activity of this pathway after nicotine exposure. Additionally, RasGRF2 KO mice demonstrated increased self-administration of nicotine compared to WT mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Geoff P. O'Donoghue, Lukasz J. Bugaj, Warren Anderson, Kyle G. Daniels, David J. Rawlings, Wendell A. Lim
Summary: T cells are able to pick out antigenic signals and establish self-tolerance from complex temporal patterns of stimulus. By engineering T cells to respond to light as a stimulus, researchers found that T cells can filter out minute-scale oscillations of activation signal. CD69 expression reached a local minimum at a period of around 25 minutes, suggesting a potential frequency filtering mechanism downstream of the Erk signaling branch. This study highlights the ability of T cell signaling machinery to temporally filter and interpret time-variant input signals in discriminatory ways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Geoff P. O'Donoghue, Lukasz J. Bugaj, Warren Anderson, Kyle G. Daniels, David J. Rawlings, Wendell A. Lim
Summary: T cells experience complex temporal patterns of stimulation through receptor-ligand-binding interactions with surrounding cells, enabling them to pick out antigenic signals and establish self-tolerance. This study demonstrates that T cells are able to respond to minute-scale oscillations of activation signal and interpret time-variant input signals through a frequency filtering mechanism downstream of the Erk signaling branch. Temporal filtering may play a functional role in vivo, as indicated by observed T cell encounters with self-peptide-presenting antigen-presenting cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Peng Liu, Liwei Zhao, Laurence Zitvogel, Oliver Kepp, Guido Kroemer
Summary: The search for immunostimulatory drugs in cancer immunotherapy can benefit from target-agnostic methods that screen agents for their functional impact on immune cells cultured in vitro without preconceived notions of their mode of action. A synthetic mini-immune system has been developed to confront stressed and dying cancer cells with dendritic cells (DCs) and CD8(+) T-cell hybridoma cells. This system can identify three types of immunostimulatory drugs: those that stimulate immunogenic cell death (ICD) of cancer cells, drugs that enhance DC response to ICD, and drugs that increase T cell effector function. Strategies to develop ICD enhancers are discussed, including ligands of pattern recognition receptors and immunometabolic modifiers, as well as methods for target deconvolution.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Peripheral Vascular Disease
Akiko Hiramatsu, Yuichiro Izumi, Koji Eguchi, Naomi Matsuo, Qinyuan Deng, Hideki Inoue, Yushi Nakayama, Hiroshi Nonoguchi, Jose Aramburu, Cristina Lopez-Rodriguez, Yutaka Kakizoe, Masataka Adachi, Takashige Kuwabara, Shokei Kim-Mitsuyama, Masashi Mukoyama
Summary: The study showed that renal tubular NFAT5 plays an important role in regulating sodium reabsorption through the epithelial sodium channel under high-salt conditions, thereby preventing salt-dependent hypertension.
Article
Cell Biology
Jiri Koutnik, Verena Neururer, Thomas Gruber, Sebastian Peer, Natascha Hermann-Kleiter, William J. Olson, Verena Labi, Michael Leitges, Gottfried Baier, Kerstin Siegmund
Summary: The deficiency of PKD3 leads to a skewing of T cell compartment towards an activated phenotype in mice, but it is dispensable for naive CD4(+) T cell differentiation in vitro.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biology
Julia Eve Olivieri, Roozbeh Dehghannasiri, Peter L. Wang, SoRi Jang, Antoine de Morree, Serena Y. Tan, Jingsi Ming, Angela Ruohao Wu, Tabula Sapiens Consortium, Stephen R. Quake, Mark A. Krasnow, Julia Salzman
Summary: The study utilized a new statistical approach called SpliZ to detect and validate cell-type-specific splicing in multiple human tissues, demonstrating that splicing is regulated at the level of cell type.
Article
Immunology
Lauren E. Higdon, Claire E. Gustafson, Xuhuai Ji, Malaya K. Sahoo, Benjamin A. Pinsky, Kenneth B. Margulies, Holden T. Maecker, Jorg Goronzy, Jonathan S. Maltzman
Summary: Immune function changes with age, and infection with CMV accelerates these changes, resulting in increased mortality and impaired responses in elderly individuals. Following organ transplantation, CMV+ recipients show accelerated aging of CD8 T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Paolo Cravedi, Patrick Ahearn, Lin Wang, Tanuja Yalamarti, Susan Hartzell, Yorg Azzi, Madhav C. Menon, Aditya Jain, Marzuq Billah, Marcelo Fernandez-Vina, Howard M. Gebel, E. Steve Woodle, Natalie S. Haddad, Andrea Morrison-Porter, F. Eun-Hyung Lee, Ignacio Sanz, Enver Akalin, Alin Girnita, Jonathan S. Maltzman
Summary: The study found that kidney transplant recipients have delayed IgG responses to SARS-CoV-2, while IgA and IgM responses are similar to immunocompetent controls. This may explain the poor outcomes in transplant recipients with COVID-19.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Sevahn K. Vorperian, Mira N. Moufarrej, Stephen R. Quake
Summary: Cell types affected by diseases can be identified by analyzing cell-free RNA, allowing the determination of their tissue of origin. By utilizing various databases and transcriptomic cell atlases, cell type signature scores can be used to infer cell types contributing to cell-free RNA in different diseases.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Robert C. Jones, Jim Karkanias, Mark A. Krasnow, Angela Oliveira Pisco, Stephen R. Quake, Julia Salzman, Nir Yosef, Bryan Bulthaup, Phillip Brown, William Harper, Marisa Hemenez, Ravikumar Ponnusamy, Ahmad Salehi, Bhavani A. Sanagavarapu, Eileen Spallino, Waldo Concepcion, Ksenia A. Aaron, James M. Gardner, Burnett Kelly, Nikole Neidlinger, Zifa Wang, Sheela Crasta, Saroja Kolluru, Maurizio Morri, Serena Y. Tan, Kyle J. Travaglini, Chenling Xu, Marcela Alcantara-Hernandez, Nicole Almanzar, Jane Antony, Benjamin Beyersdorf, Deviana Burhan, Kruti Calcuttawala, Matthew M. Carter, Charles K. F. Chan, Charles A. Chang, Stephen Chang, Alex Colville, Rebecca N. Culver, Gaetano D'Amato, Camille Ezran, Francisco X. Galdos, Astrid Gillich, William R. Goodyer, Yan Hang, Alyssa Hayashi, Sahar Houshdaran, Xianxi Huang, Juan C. Irwin, SoRi Jang, Julia Vallve Juanico, Aaron M. Kershner, Soochi Kim, Bernhard Kiss, William Kong, Maya E. Kumar, Angera H. Kuo, Rebecca Leylek, Baoxiang Li, Gabriel B. Loeb, Wan-Jin Lu, Sruthi Mantri, Maxim Markovic, Patrick L. McAlpine, Antoine de Morree, Karim Mrouj, Shravani Mukherjee, Tyler Muser, Patrick Neuhofer, Thi D. Nguyen, Kimberly Perez, Ragini Phansalkar, Nazan Puluca, Zhen Qi, Poorvi Rao, Hayley Raquer-McKay, Nicholas Schaum, Bronwyn Scott, Bobak Seddighzadeh, Joe Segal, Sushmita Sen, Shaheen Sikandar, Sean P. Spencer, Lea C. Steffes, Varun R. Subramaniam, Aditi Swarup, Michael Swift, Will Van Treuren, Emily Trimm, Stefan Veizades, Sivakamasundari Vijayakumar, Kim Chi Vo, Sevahn K. Vorperian, Wanxin Wang, Hannah N. W. Weinstein, Juliane Winkler, Timothy T. H. Wu, Jamie Xie, Andrea R. Yung, Yue Zhang, Angela M. Detweiler, Honey Mekonen, Norma F. Neff, Rene Sit, Michelle Tan, Jia Yan, Gregory R. Bean, Vivek Charu, Erna Forgo, Brock A. Martin, Michael G. Ozawa, Oscar Silva, Angus Toland, Venkata N. P. Vemuri, Shaked Afik, Kyle Awayan, Olga Borisovna Botvinnik, Ashley Byrne, Michelle Chen, Roozbeh Dehghannasiri, Adam Gayoso, Alejandro A. Granados, Qiqing Li, Gita Mahmoudabadi, Aaron McGeever, Julia Eve Olivieri, Madeline Park, Neha Ravikumar, Geoff Stanley, Weilun Tan, Alexander J. Tarashansky, Rohan Vanheusden, Peter Wang, Sheng Wang, Galen Xing, Rebecca Culver, Les Dethlefsen, Po-Yi Ho, Shixuan Liu, Jonathan S. Maltzman, Ross J. Metzger, Koki Sasagawa, Rahul Sinha, Hanbing Song, Bruce Wang, Steven E. Artandi, Philip A. Beachy, Michael F. Clarke, Linda C. Giudice, Franklin W. Huang, Kerwyn Casey Huang, Juliana Idoyaga, Seung K. Kim, Mark Krasnow, Christin S. Kuo, Patricia Nguyen, Thomas A. Rando, Kristy Red-Horse, Jeremy Reiter, David A. Relman, Justin L. Sonnenburg, Albert Wu, Sean M. Wu, Tony Wyss-Coray
Summary: The molecular characterization of cell types using single-cell transcriptome sequencing has led to a revolution in cell biology and provided new insights into the physiology of human organs. In this study, a human reference atlas was created, consisting of nearly 500,000 cells from 24 different tissues and organs, allowing for the molecular characterization of over 400 cell types, their tissue distribution, and tissue-specific variation in gene expression. By using multiple tissues from the same donor, the clonal distribution of T cells, tissue-specific mutation rate in B cells, and the analysis of cell cycle state and proliferative potential of shared cell types across tissues were identified. Additionally, cell type-specific RNA splicing was discovered and analyzed within an individual.
Editorial Material
Urology & Nephrology
Caroline Lamarche, Jonathan S. Maltzman
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Immunology
Lauren E. Higdon, Ayah A. Ahmad, Steven Schaffert, Kenneth B. Margulies, Jonathan S. Maltzman
Summary: This study investigated the impact of CMV infection on the differentiation, functionality, and expansion of CD4 T cells in transplant recipients in the first year post-transplant. The findings suggest that the CD4 response to CMV is dominated by cytotoxicity and remains stable in the first year after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Zeguo Sun, Zhongyang Zhang, Khadija Banu, Yorg Al Azzi, Anand Reghuvaran, Samuel Fredericks, Marina Planoutene, Susan Hartzell, Yesl Kim, John Pell, Gregory Tietjen, William Asch, Sanjay Kulkarni, Richard Formica, Meenakshi Rana, Jonathan S. S. Maltzman, Weijia Zhang, Enver Akalin, Peter S. S. Heeger, Paolo Cravedi, Madhav C. C. Menon
Summary: The study found that during acute COVID-19, the blood transcriptome of KTRs showed a decrease in T cell and adaptive immune activation pathways, despite reduced use of immunosuppressants. These pathways recovered after acute illness. The findings provide an explanation for immune insufficiency in KTRs during acute COVID-19.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Immunology
Alin L. Girnita, Lin Wang, Adriana Colovai, Patrick Ahearn, Yorg Azzi, Madhav C. Menon, Marcelo Fernandez-Vina, Howard M. Gebel, E. Steve Woodle, Paolo Cravedi, Jonathan S. Maltzman, Enver Akalin
Summary: This study investigated the changes in anti-HLA antibodies in kidney transplant recipients after COVID-19 and compared them with anti-SARS-CoV-2 antibodies. The results showed that anti-HLA antibodies were mainly IgG, while anti-SARS-CoV-2 antibodies had a high IgA/IgM profile.
Review
Immunology
Lauren E. Higdon, Jane C. Tan, Jonathan S. Maltzman
Summary: Solid organ transplantation is a life-saving treatment for end-stage organ disease, but immune-mediated transplant rejection poses a common complication. Immunosuppression is necessary to prevent rejection, but it increases the risk of infection. Certain infections like cytomegalovirus and BK virus can promote inflammatory gene expression, leading to rejection. Moreover, viral infections can complicate accurate diagnosis and induce rejection through heterologous immunity. Understanding the interplay between viral infections and allograft rejection is important for long-term transplant survival.
Letter
Urology & Nephrology
Gianluigi Zaza, Giovanni Stallone, Simona Granata, Micaela Gentile, Maddalena Panico, Sofia Bin, Lin Wang, Christiane Rollenhagen, Jonathan S. Maltzman, Paolo Cravedi
KIDNEY INTERNATIONAL REPORTS
(2023)
Article
Immunology
Darshana M. Dadhania, Paolo Cravedi, Emily Blumberg, Gabriel Stryniak, Maria E. Montez-Rath, Jonathan S. Maltzman
Summary: This study investigated the maintenance of immunity in kidney transplant recipients after Hepatitis B virus vaccination. The results showed that age and immunosuppression influenced the level of immunity after vaccination. Older patients had a significant decline in immunity post-transplantation.
TRANSPLANT INFECTIOUS DISEASE
(2023)
Article
Surgery
Christiane Rollenhagen, Jonathan S. Maltzman
Summary: This review discusses how T, natural killer (NK), and B cell aging impacts outcomes of organ transplantation, the recipient's response to vaccines, susceptibility to latent viral infections, and organ quality and function. Aging immune system is characterized by a decline in naive T cells, an increase in memory T cells expressing innate markers, a decline in NK cell cytokine secretion, cytotoxicity, and immune recognition, as well as expansion of age-associated pro-inflammatory B lymphocytes (ABCs). Functional changes in aged immune cells contribute to inflammation and impair their ability to control infections, mount vaccine responses, and lead to allorejection.
CURRENT TRANSPLANTATION REPORTS
(2023)
Article
Urology & Nephrology
Xiaoyi Zheng, Lauren Higdon, Alexandre Gaudet, Manav Shah, Angela Balistieri, Catherine Li, Patricia Nadai, Latha Palaniappan, Xiaoping Yang, Briana Santo, Brandon Ginley, Xiaoxin X. Wang, Komuraiah Myakala, Pratima Nallagatla, Moshe Levi, Pinaki Sarder, Avi Rosenberg, Jonathan S. Maltzman, Nathalie de Freitas Caires, Vivek Bhalla
Summary: This study demonstrates the important protective role of Esm-1 in diabetic kidney disease, inhibiting the development of the disease by reducing albuminuria and podocyte injury, possibly through interferon signaling pathways.
Article
Immunology
Lucrezia Furian, Francesco Paolo Russo, Gianluigi Zaza, Patrizia Burra, Susan Hartzell, Debora Bizzaro, Marianna Di Bello, Caterina Di Bella, Erica Nuzzolese, Clara Agnolon, Sander Florman, Meenakshi Rana, Jar-How Lee, Yesl Kim, Umberto Maggiore, Jonathan S. Maltzman, Paolo Cravedi
Summary: The antibody and T cell responses after SARS-CoV-2 vaccination were compared between kidney and liver transplant recipients. It was found that liver transplant recipients had a stronger immune response than kidney transplant recipients, which was not solely explained by differences in immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)