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Efficacy against Lung Cancer Is Augmented by Combining Aberrantly N-Glycosylated T Cells with a Chimeric Antigen Receptor Targeting Fragile X Mental Retardation 1 Neighbor J. Immunol. (IF 4.4) Pub Date : 2024-01-12 Toshihiko Toyofuku, Takako Ishikawa, Satoshi Nojima, Atsushi Kumanogoh
Abstract The adaptive transfer of T cells redirected to cancer cells via chimeric Ag receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to solid cancer, we screened CARs targeting surface Ags on human lung cancer cells using (to our knowledge) novel expression cloning based on the Ag receptor-induced transcriptional activation of IL-2
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Development of a New Off-the-Shelf Plasmacytoid Dendritic Cell–Based Approach for the Expansion and Characterization of SARS-CoV-2–Specific T Cells J. Immunol. (IF 4.4) Pub Date : 2024-01-12 Anthony Maino, Axelle Amen, Joël Plumas, Lucie Bouquet, Marina Deschamps, Philippe Saas, Laurence Chaperot, Olivier Manches
Abstract Global vaccination against COVID-19 has been widely successful; however, there is a need for complementary immunotherapies in severe forms of the disease and in immunocompromised patients. Cytotoxic CD8+ T cells have a crucial role in disease control, but their function can be dysregulated in severe forms of the disease. We report here a cell-based approach using a plasmacytoid dendritic cell
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USP13 Cooperates with MARCH8 to Inhibit Antiviral Signaling by Targeting MAVS for Autophagic Degradation in Teleost J. Immunol. (IF 4.4) Pub Date : 2024-01-12 Pengfei Wang, Yuena Sun, Tianjun Xu
Abstract Mitochondrial antiviral signaling protein (MAVS), as a central adapter protein in retinoic acid–inducible gene I–like receptor signaling, is indispensable for innate antiviral immunity. Yet, the molecular mechanisms modulating the stability of MAVS are not fully understood in low vertebrates. In this study, we report that the deubiquitinase ubiquitin-specific protease 13 (USP13) acts as a
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Cutting Edge: Characterization of Low Copy Number Human Angiotensin-Converting Enzyme 2–Transgenic Mice as an Improved Model of SARS-CoV-2 Infection J. Immunol. (IF 4.4) Pub Date : 2024-01-10 Christine M. Bradshaw, Teodora Georgieva, Trevor N. Tankersley, Tama Taylor-Doyle, Larry Johnson, Jennifer L. Uhrlaub, David Besselsen, Janko Ž. Nikolich
Abstract A popular mouse model of COVID-19, the K18-hACE2 mouse, expresses the SARS-coronavirus entry receptor, human angiotensin-converting enzyme 2 (hACE2) driven by the keratin-18 promoter. SARS-CoV-2–infected K18-hACE2 mice exhibit neuropathology not representative of human infection. They contain eight transgene (Tg) copies, leading to excess hACE2 expression and rampant viral replication. We
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Butyrate, Valerate, and Niacin Ameliorate Anaphylaxis by Suppressing IgE-Dependent Mast Cell Activation: Roles of GPR109A, PGE2, and Epigenetic Regulation J. Immunol. (IF 4.4) Pub Date : 2024-01-10 Kazuki Nagata, Daisuke Ando, Tsubasa Ashikari, Kandai Ito, Ryosuke Miura, Izumi Fujigaki, Yuki Goto, Miki Ando, Naoto Ito, Hibiki Kawazoe, Yuki Iizuka, Mariko Inoue, Takuya Yashiro, Masakazu Hachisu, Kazumi Kasakura, Chiharu Nishiyama
Abstract Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during the fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate the development and function of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) remain unclear. In the current study, we analyzed the function and gene
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Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer J. Immunol. (IF 4.4) Pub Date : 2024-01-10 Bingyu Wang, Zhonghao Mao, Jinwen Ye, Xinlin Jiao, Teng Zhang, Qi Wang, Sai Han, Youzhong Zhang, Chunling Wang, Taotao Dong, Baoxia Cui
Abstract N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role in various biological processes. However, the roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated in the tumor microenvironment of cervical cancer, are still unclear. We analyzed the abnormal m6A methylation in cervical cancer, using CaSki and THP-1 cell lines
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Vaccine Molecule Design Based on Phage Display and Computational Modeling against Rhabdovirus J. Immunol. (IF 4.4) Pub Date : 2024-01-10 Yu-Ying Zheng, Liang Zhao, Xue-Feng Wei, Tian-Zi Sun, Fei-Fan Xu, Gao-Xue Wang, Bin Zhu
Abstract Rhabdoviruses with rich species lead a variety of high lethality and rapid transmission diseases to plants and animals around the globe. Vaccination is one of the most effective approaches to prevent and control virus disease. However, the key antigenic epitopes of glycoprotein being used for vaccine development are unclear. In this study, fish-derived Abs are employed for a Micropterus salmoides
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Memory-like NK Cells Are a Critical Component of Vaccine-Induced Immunity to Trypanosoma cruzi Infection J. Immunol. (IF 4.4) Pub Date : 2024-01-10 Aline L. Horta, Jason Gigley, Marie Boutet, Gregoire Lavau, Louis M. Weiss, Huan Huang
Abstract Chagas disease by Trypanosoma cruzi infection is a major public health issue. The available therapeutic agents have limited efficacy and significant side effects. A reliable vaccine would reduce the threat of T. cruzi infections and prevent Chagas disease. Understanding the immune response to this infection would improve vaccine design. We previously demonstrated that adoptively transferred
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Reduced Expression of miR-146a Potentiates Intestinal Inflammation following Alcohol and Burn Injury J. Immunol. (IF 4.4) Pub Date : 2024-01-08 Caroline J. Herrnreiter, Marisa E. Luck, Abigail R. Cannon, Xiaoling Li, Mashkoor A. Choudhry
Abstract MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis, and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA
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Engineering Anticytokine Antibodies for Immune Modulation J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Jakub Tomala, Shanelle D. Cao, Jamie B. Spangler
Abstract The delicate balance of immune homeostasis is regulated by the interactions between cytokines and their cognate cell surface signaling receptors. There is intensive interest in harnessing cytokines as drugs for diseases such as cancer and autoimmune disorders. However, the multifarious and often contradictory activities of cytokines, coupled with their short serum half-lives, limit clinical
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Rational Engineering of Islet Tolerance via Biomaterial-Mediated Immune Modulation J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Natalie Klug, Jacqueline Burke, Evan Scott
Abstract Type 1 diabetes (T1D) onset is characterized by an autoimmune attack on β islet cells within the pancreas, preventing the insulin secretion required to maintain glucose homeostasis. Targeted modulation of key immunoregulatory cell populations is a promising strategy to restore tolerance to β cells. This strategy can be used to prevent T1D onset or reverse T1D with transplanted islets. To this
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Microengineered In Vitro Assays for Screening and Sorting Manufactured Therapeutic T Cells J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Abir K. Muhuri, Yunus Alapan, Camila P. Camargo, Susan N. Thomas
Abstract Adoptively transferred T cells constitute a major class of current and emergent cellular immunotherapies for the treatment of disease, including but not limited to cancer. Although key advancements in molecular recognition, genetic engineering, and manufacturing have dramatically enhanced their translational potential, therapeutic potency remains limited by poor homing and infiltration of
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Materials-Based Approaches for Cancer Vaccination J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Miguel C. Sobral, David J. Mooney
Abstract Therapeutic cancer vaccines offer the promise of stimulating the immune system to specifically eradicate tumor cells and establish long-term memory to prevent tumor recurrence. However, despite showing benign safety profiles and the ability to generate Ag-specific cellular responses, cancer vaccines have been hampered by modest clinical efficacy. Lessons learned from these studies have led
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Modulating Antigen Availability in Lymphoid Organs to Shape the Humoral Immune Response to Vaccines J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Aereas Aung, Darrell J. Irvine
Abstract Primary immune responses following vaccination are initiated in draining lymph nodes, where naive T and B cells encounter Ag and undergo coordinated steps of activation. For humoral immunity, the amount of Ag present over time, its localization to follicles and follicular dendritic cells, and the Ag’s structural state all play important roles in determining the subsequent immune response.
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Top Reads J. Immunol. (IF 4.4) Pub Date : 2024-01-15
NADPH Oxidase 2 ROS Promote CD8 T Cell Function See article p. 258 Analysis of γδ T Cells from Human Spleen See article p. 284
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Engineering Strategies to Modulate the Gut Microbiome and Immune System J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Kai Han, Jin Xu, Fang Xie, Julia Crowther, James J. Moon
Abstract The gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral
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Engineering Challenges and Opportunities in Autologous Cellular Cancer Immunotherapy J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Colleen R. Foley, Sheridan L. Swan, Melody A. Swartz
Abstract The use of a patient’s own immune or tumor cells, manipulated ex vivo, enables Ag- or patient-specific immunotherapy. Despite some clinical successes, there remain significant barriers to efficacy, broad patient population applicability, and safety. Immunotherapies that target specific tumor Ags, such as chimeric Ag receptor T cells and some dendritic cell vaccines, can mount robust immune
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Advancing Antibody Engineering through Synthetic Evolution and Machine Learning J. Immunol. (IF 4.4) Pub Date : 2024-01-15 Edward B. Irvine, Sai T. Reddy
Abstract Abs are versatile molecules with the potential to achieve exceptional binding to target Ags, while also possessing biophysical properties suitable for therapeutic drug development. Protein display and directed evolution systems have transformed synthetic Ab discovery, engineering, and optimization, vastly expanding the number of Ab clones able to be experimentally screened for binding. Moreover
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Recruitment and Maintenance of CX3CR1+CD4+ T Cells during Helminth Infection J. Immunol. (IF 4.4) Pub Date : 2024-01-05 Denis G. Loredan, Joseph C. Devlin, Kamal M. Khanna, P’ng Loke
Abstract Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+CD4+ T cells during type 2 inflammation in helminth infections. In this study, we used a fate-mapping mouse model to characterize CX3CR1+CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni murine models of helminth infections, revealing CX3CR1+CD4+
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Antiviral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models J. Immunol. (IF 4.4) Pub Date : 2024-01-05 Nisha Rajeswari Dhanushkodi, Swayam Prakash, Afshana Quadiri, Latifa Zayou, Ruchi Srivastava, Amin Mohammed Shaik, Berfin Suzer, Izabela Coimbra Ibraim, Gary Landucci, Delia F. Tifrea, Mahmoud Singer, Leila Jamal, Robert A. Edwards, Hawa Vahed, Lawrence Brown, Lbachir BenMohamed
Abstract SARS-CoV-2 variants of concern (VOCs) continue to evolve and reemerge with chronic inflammatory long COVID sequelae, necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the receptor for advanced glycation end products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of RAGE in COVID-19 has not been reported. In the
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CL-K1 Promotes Complement Activation and Regulates Opsonophagocytosis of Macrophages with CD93 Interaction in a Primitive Vertebrate J. Immunol. (IF 4.4) Pub Date : 2024-01-05 Liangliang Mu, Xiaoxue Yin, Li Qiu, Jiadong Li, Jinfen Mo, Hao Bai, Qingliang Zeng, Jianmin Ye
Abstract Collectin is a crucial component of the innate immune system and plays a vital role in the initial line of defense against pathogen infection. In mammals, collectin kidney 1 (CL-K1) is a soluble collectin that has recently been identified to have significant functions in host defense. However, the evolutionary origins of immune defense of CL-K1 and its mechanism in clearance of pathogenic
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Schistosome Infection Impacts Hematopoiesis J. Immunol. (IF 4.4) Pub Date : 2024-01-03 Tobias Wijshake, Joseph Rose, Jipeng Wang, Jacob Zielke, Madeleine Marlar-Pavey, Weina Chen, James J. Collins, Michalis Agathocleous
Abstract Helminth infections are common in animals. However, the impact of a helminth infection on the function of hematopoietic stem cells (HSCs) and other hematopoietic cells has not been comprehensively defined. In this article, we describe the hematopoietic response to infection of mice with Schistosoma mansoni, a parasitic flatworm that causes schistosomiasis. We analyzed the frequency or number
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Corrections: A2B adenosine receptor expression by myeloid cells is pro-inflammatory in murine allergic-airway inflammation J. Immunol. (IF 4.4) Pub Date : 2024-01-03 Bryan G Belikoff, Louis J Vaickus, Michail Sitkovsky, Daniel G Remick
Abstract Belikoff, B. G., L. J. Vaickus, M. Sitkovsky, and D. G. Remick. 2012. A2B adenosine receptor expression by myeloid cells is pro-inflammatory in murine allergic-airway inflammation. J. Immunol. 189: 3707–3713. Two of the panels in Fig. 2C (the histology photomicrographs for wild type and A2B receptor knockout) were inadvertently duplicated. Due to the age of the article, the authors no longer
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Histone Deacetylase Inhibitors Directly Modulate T Cell Gene Expression and Signaling and Promote Development of Effector-Exhausted T Cells in Murine Tumors J. Immunol. (IF 4.4) Pub Date : 2024-01-03 Mohammed L. Ibrahim, Hong Zheng, Margaret L. Barlow, Yousuf Latif, Zhihua Chen, Xiaoqing Yu, Amer A. Beg
Abstract Epigenetic regulation plays a crucial role in the development and progression of cancer, including the regulation of antitumor immunity. The reversible nature of epigenetic modifications offers potential therapeutic avenues for cancer treatment. In particular, histone deacetylase (HDAC) inhibitors (HDACis) have been shown to promote antitumor T cell immunity by regulating myeloid cell types
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A Lipopolysaccharide-Enriched Cow’s Milk Allergy Microbiome Promotes a TLR4-Dependent Proinflammatory Intestinal Immune Response J. Immunol. (IF 4.4) Pub Date : 2024-01-03 Evelyn Campbell, Lauren A. Hesser, Roberto Berni Canani, Laura Carucci, Lorella Paparo, Robert T. Patry, Cathryn R. Nagler
Abstract We have previously reported that the gut microbiota of healthy infants harbors allergy-protective bacteria taxa that are depleted in infants with cow’s milk allergy (CMA). Few reports have investigated the role of the gut microbiota in promoting allergic responses. In this study we selected a CMA-associated microbiota with increased abundance of Gram-negative bacteria for analysis of its proinflammatory
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IFN-β Pretreatment Alleviates Allogeneic Renal Tubular Epithelial Cell–Induced NK Cell Responses via the IRF7/HLA-E/NKG2A Axis J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Xing Zhang, Junni Wang, Mowang Wang, Mengbao Du, Jianghua Chen, Limengmeng Wang, Jianyong Wu
Abstract Immune checkpoint molecules are promising targets for suppressing the immune response but have received little attention in immune tolerance induction in organ transplantation. In this study, we found that IFN-β could induce the expression of HLA-E as well as PD-L1 on human renal tubular epithelial cell line HK-2 and renal tissue of the C57BL/6 mouse. The JAK/STAT2 pathway was necessary for
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Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Xin Xu, Timothy J. Herdendorf, Huiquan Duan, Denise L. Rohlik, Sourav Roy, Hinman Zhou, Haya Alkhateeb, Sanjay Khandelwal, Qilong Zhou, Ping Li, Gowthami M. Arepally, John K. Walker, Brandon L. Garcia, Brian V. Geisbrecht
Abstract The classical pathway (CP) is a potent mechanism for initiating complement activity and is a driver of pathology in many complement-mediated diseases. The CP is initiated via activation of complement component C1, which consists of the pattern recognition molecule C1q bound to a tetrameric assembly of proteases C1r and C1s. Enzymatically active C1s provides the catalytic basis for cleavage
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Cross-Reactivity of Antibodies to Rituximab with Other Therapeutic Anti-CD20 Antibodies J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Theo Rispens, Taco W. Kuijpers, Joep Killestein, Zoé L. E. van Kempen, Karien Bloem
Abstract One reason for a lack of response to rituximab as well as infusion-related anaphylactic adverse events is the development of antidrug Abs to rituximab. Besides rituximab, a number of other therapeutic Abs targeting CD20 are nowadays available as alternatives. In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab
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The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Mallika Ghosh, Fraser McGurk, Rachael Norris, Andy Dong, Sreenidhi Nair, Evan Jellison, Patrick Murphy, Rajkumar Verma, Linda H. Shapiro
Abstract Implanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs)
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Defining Parameters That Modulate Susceptibility and Protection to Respiratory Murine Coronavirus MHV1 Infection J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Elvia E. Silva, Steven J. Moioffer, Mariah Hassert, Roger R. Berton, Matthew G. Smith, Stephanie van de Wall, David K. Meyerholz, Thomas S. Griffith, John T. Harty, Vladimir P. Badovinac
Abstract Patients infected with SARS-CoV-2 experience variable disease susceptibility, and patients with comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines disease outcomes and whether this can be used for immunological priming in a genetically susceptible host has not been completely defined. We used
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Effector-Phase IL-2 Signals Drive Th1 Effector and Memory Responses Dependently and Independently of TCF-1 J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Krystal R. Charley, Andrew G. Ramstead, Joseph G. Matous, Yohichi Kumaki, Linda M. Sircy, J. Scott Hale, Matthew A. Williams
Abstract Following viral infection, CD4+ T cell differentiation is tightly regulated by cytokines and TCR signals. Although most activated CD4+ T cells express IL-2Rα after lymphocytic choriomeningtis virus infection, by day 3 postinfection, only half of activated T cells maintain expression. IL-2Rα at this time point distinguishes precursors for terminally differentiated Th1 cells (IL-2Rαhi) from
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Inherently Reduced Expression of ASC Restricts Caspase-1 Processing in Hepatocytes and Promotes Plasmodium Infection J. Immunol. (IF 4.4) Pub Date : 2023-12-27 Camila Marques-da-Silva, Clyde Schmidt-Silva, Rodrigo P. Baptista, Samarchith P. Kurup
Abstract Inflammasome-mediated caspase-1 activation facilitates innate immune control of Plasmodium in the liver, thereby limiting the incidence and severity of clinical malaria. However, caspase-1 processing occurs incompletely in both mouse and human hepatocytes and precludes the generation of mature IL-1β or IL-18, unlike in other cells. Why this is so or how it impacts Plasmodium control in the
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The CATERPILLERS J. Immunol. (IF 4.4) Pub Date : 2024-01-01 Amal O. Amer
This Pillars of Immunology article is a commentary on “Cutting Edge: CATERPILLER: A large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains,” a pivotal article written by J. A. Harton, M. W. Linhoff, J. Zhang, and J. P.-Y. Ting,” and published in The Journal of Immunology, in 2002. https://doi.org/10.4049/jimmunol.169.8.4088.
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Top Reads J. Immunol. (IF 4.4) Pub Date : 2024-01-01
Partitioned Hexose Influx Promotes B Cell to PC Transition See article p. 43 Cellular Immunity Limits T Cell Memory Formation After LAIV See article p. 107
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Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Henrique B. Abdalla, Luciano Puhl, Carla Alvarez Rivas, Yu-Chiao Wu, Paola Rojas, Carlos Antonio Trindade-da-Silva, Bruce D. Hammock, Krishna R. Maddipati, Mariana Q. S. Soares, Juliana T. Clemente-Napimoga, Alpdogan Kantarci, Marcelo H. Napimoga, Thomas E. Van Dyke
Abstract Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental
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Single-Cell Transcriptomes and Immune Repertoires Reveal the Cell State and Molecular Changes in Pemphigus Vulgaris J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Shumin Duan, Qionghua Li, Fei Wang, Wenjing Kuang, Yunmei Dong, Dan Liu, Jiongke Wang, Wei Li, Qianming Chen, Xin Zeng, Taiwen Li
Abstract The etiology and pathogenesis of pemphigus vulgaris (PV) entail intricate interactions between immune cells and epithelial cells. However, the specific subtypes of immune cells involved in PV, along with their respective roles, remain elusive. Likewise, the precise functions and mechanisms by which glucocorticoids affect cell types within the disease context require further elucidation. To
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Cutting Edge: PDGF-DD Binding to NKp44 Costimulates TLR9 Signaling and Proinflammatory Cytokine Secretion in Human Plasmacytoid Dendritic Cells J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Alexander David Barrow, Marina Cella, Melissa Anne Edeling, Md. Abdullah-Al-Kamran Khan, Luisa Cervantes-Barragan, Mattia Bugatti, Christian Schmedt, William Vermi, Marco Colonna
Abstract NKp44 is a human receptor originally found on activated NK cells, group 1 and group 3 innate lymphoid cells that binds dimers of platelet-derived growth factor D (PDGF-DD). NKp44 is also expressed on tissue plasmacytoid dendritic cells (PDCs), but NKp44-PDGF-DD interaction on PDCs remains unstudied. Engagement of NKp44 with PDGF-DD in vitro enhanced PDC secretion of IFN-α, TNF, and IL-6 in
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CHTOP Promotes Microglia-Mediated Inflammation by Regulating Cell Metabolism and Inflammatory Gene Expression J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Xin Zhou, Mengfei Lv, Zhongying Duan, Wenhao Liu, Feng Yan, Jiake Liu, Yu Cui
Abstract During the initiation of the inflammatory response of microglia, the expression of many inflammation- and cell metabolism–related genes alters. However, how the transcription of inflammation- and metabolism-related genes are coordinately regulated during inflammation initiation is poorly understood. In this study, we found that LPS stimulation induced the expression of the chromatin target
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A Bacterial and Ganglioside-based Nanoparticle Initiates Reprogramming of Macrophages and Promotes Antitumor Phenotypes J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Rydell Alvarez-Arzola, Liliana Oliver, Michelle M. Messmer, Danielle Y.F. Twum, Kelvin P. Lee, Jason B. Muhitch, Circe Mesa, Scott I. Abrams
Abstract Macrophages represent the most abundant immune component of the tumor microenvironment and often exhibit protumorigenic (M2-like) phenotypes that contribute to disease progression. Despite their generally accepted protumorigenic role, macrophages can also display tumoricidal (or M1-like) behavior, revealing that macrophages can be functionally reprogrammed, depending on the cues received within
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Alternatively Spliced Variants of Murine CD247 Influence T Cell Development and Activation, Revealing the Importance of the CD3ζ C-Terminal Region J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Ye Jin, Huijuan Yuan, Isha Mehta, Ogechukwu Ezenwa, Penelope A. Morel
Abstract CD247, also known as CD3ζ, is a crucial signaling molecule that transduces signals delivered by TCR through its three ITAMs. CD3ζ is required for successful thymocyte development. Three additional alternatively spliced variants of murine CD247 have been described, that is, CD3ι, CD3θ, and CD3η, that differ from CD3ζ in the C terminus such that the third ITAM is lost. Previous studies demonstrated
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The Cyclin D3 Protein Enforces Monogenic TCRβ Expression by Mediating TCRβ Protein–Signaled Feedback Inhibition of Vβ Recombination J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Erica J. Culberson, Kymberle C. Shields, Rebecca A. Glynn, Brittney M. Allyn, Katharina E. Hayer, Craig H. Bassing
Abstract In jawed vertebrates, adaptive immunity depends on the process of V(D)J recombination creating vast numbers of T and B lymphocytes that each expresses unique Ag receptors of uniform specificity. The asynchronous initiation of V-to-(D)J rearrangement between alleles and the resulting protein from one allele signaling feedback inhibition of V recombination on the other allele ensures homogeneous
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Dynamic MAIT Cell Recovery after Severe COVID-19 Is Transient with Signs of Heterogeneous Functional Anomalies J. Immunol. (IF 4.4) Pub Date : 2023-12-20 Tobias Kammann, Jean-Baptiste Gorin, Tiphaine Parrot, Yu Gao, Andrea Ponzetta, Johanna Emgård, Kimia T. Maleki, Takuya Sekine, Olga Rivera-Ballesteros, Sara Gredmark-Russ, Olav Rooyackers, Magdalena Skagerberg, Lars I. Eriksson, Anna Norrby-Teglund, Jeffrey Y.W. Mak, David P. Fairlie, Niklas K. Björkström, Jonas Klingström, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Kristoffer Strålin, Johan
Abstract Mucosal-associated invariant T (MAIT) cells are an abundant population of unconventional T cells in humans and play important roles in immune defense against microbial infections. Severe COVID-19 is associated with strong activation of MAIT cells and loss of these cells from circulation. In the present study, we investigated the capacity of MAIT cells to recover after severe COVID-19. In longitudinal
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Tim-3 Is Not Required for Establishment of CD8+ T Cell Memory to Lymphocytic Choriomeningitis Virus J. Immunol. (IF 4.4) Pub Date : 2023-12-18 Priyanka Manandhar, Andrea L. Szymczak-Workman, Lawrence P. Kane
Abstract Tim-3 is a transmembrane protein that is best known for being highly expressed on terminally exhausted CD8+ T cells associated with chronic infection and tumors, although its expression is not limited to those settings. Tim-3 is also expressed by CD8+ T cells during acute infection and by multiple other immune cell types, including CD4+ Th1 and regulatory T cells, dendritic cells, and mast
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Stimulation Strength Determined by Superantigen Dose Controls Subcellular Localization of FOXP3 Isoforms and Suppressive Function of CD4+CD25+FOXP3+ T Cells J. Immunol. (IF 4.4) Pub Date : 2023-12-18 Juyeun Lee, Nogi Park, Michael Nicosia, Joo Youn Park, Stephen B. Pruett, Keun Seok Seo
Abstract Staphylococcal superantigens induce massive activation of T cells and inflammation, leading to toxic shock syndrome. Paradoxically, increasing evidence indicates that superantigens can also induce immunosuppression by promoting regulatory T cell (Treg) development. In this study, we demonstrate that stimulation strength plays a critical role in superantigen-mediated induction of immunosuppressive
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Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma J. Immunol. (IF 4.4) Pub Date : 2023-12-15 Jennifer Peil, Christian Vossen, Felix Bock, Thomas Clahsen, Petra Schiller, Ludwig M. Heindl, Jacobus J. Bosch, F. Thomas Wunderlich, Claus Cursiefen, Simona L. Schlereth
Abstract Angiogenesis and immune protection are essential at the onset of tumorigenesis. Angiogenesis serves to nourish the tumor, and prevention of immune defenses, for example, by dendritic cells (DCs), allows tumor growth. In this study, we investigated whether there are factors with dual functions that are both angiogenic and immunomodulatory and represent a therapeutic target. We analyzed 1) innate
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Spinal Neuronal miR-124 Inhibits Microglial Activation and Contributes to Preventive Effect of Electroacupuncture on Chemotherapy-Induced Peripheral Neuropathy in Mice J. Immunol. (IF 4.4) Pub Date : 2023-12-13 Xiao-Chen Li, Hui Chen, Yu Chen, Yu-Xia Chu, Wen-Li Mi, Yan-Qing Wang, Qi-Liang Mao-Ying
Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and irreversible side effect of antineoplastic agents. Patients with CIPN usually show chronic pain and sensory deficits with glove-and-stocking distribution. However, whether spinal neuronal microRNA (miR)-124 is involved in cisplatin-induced peripheral neuropathy remains to be studied. In this study, miR-124 was significantly
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Corrections: IL-1α mediates innate and acquired resistance to immunotherapy in melanoma. J. Immunol. (IF 4.4) Pub Date : 2023-12-13 Shubhra Singh, Zhilan Xiao, Karishma Bavisi, Jason Roszik, Brenda D Melendez, Zhiqiang Wang, Mark J Cantwell, Richard E Davis, Greg Lizee, Patrick Hwu, Sattva S Neelapu, Willem W Overwijk, Manisha Singh
Abstract Singh, S., Z. Xiao, K. Bavisi, J. Roszik, B. D. Melendez, Z. Wang, M. J. Cantwell, R. E. Davis, G. Lizee, P. Hwu, S. S. Neelapu, W. W. Overwijk, and M. Singh. 2021. IL-1α mediates innate and acquired resistance to immunotherapy in melanoma. J. Immunol. 206: 1966–1975. The Materials and Methods section erroneously omitted the manufacturer and clone of one of the Ab reagents used under the heading
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SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay J. Immunol. (IF 4.4) Pub Date : 2023-12-13 Bowen Hou, Yanyan Hu, Yuzhen Zhu, Xiaocui Wang, Wanyun Li, Jian Tang, Xian Jia, Jiayu Wang, Yu Cong, Minxue Quan, Hongying Yang, Haiping Zheng, Yuzhou Bao, Xiao Lei Chen, Hong-Rui Wang, Bing Xu, Nicholas R. J. Gascoigne, Guo Fu
Abstract SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2
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Balanced Epigenetic Regulation of MHC Class I Expression in Tumor Cells by the Histone Ubiquitin Modifiers BAP1 and PCGF1 J. Immunol. (IF 4.4) Pub Date : 2023-12-13 Ruud H. Wijdeven, Sietse J. Luk, Tom A. W. Schoufour, Sabina Y. van der Zanden, Marta Cabezuelo, Mirjam H. M. Heemskerk, Jacques Neefjes
Abstract MHC class I (MHC-I) molecules are critical for CD8+ T cell responses to viral infections and malignant cells, and tumors can downregulate MHC-I expression to promote immune evasion. In this study, using a genome-wide CRISPR screen on a human melanoma cell line, we identified the polycomb repressive complex 1 (PRC1) subunit PCGF1 and the deubiquitinating enzyme BAP1 as opposite regulators of
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NADPH Oxidase 2–Derived Reactive Oxygen Species Promote CD8+ T Cell Effector Function J. Immunol. (IF 4.4) Pub Date : 2023-12-11 Jing Chen, Chao Liu, Anna V. Chernatynskaya, Brittney Newby, Todd M. Brusko, Yuan Xu, Jessie M. Barra, Nadine Morgan, Christopher Santarlas, Westley H. Reeves, Hubert M. Tse, Jennifer W. Leiding, Clayton E. Mathews
Abstract Oxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+ CTLs. However, the molecular mechanisms impacting CD8+ T cell function remain unknown. In the present study, we examined the role of NOX2 in both NOD mouse and human CD8+ T cell function
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Top Reads J. Immunol. (IF 4.4) Pub Date : 2023-12-15
SIKs Regulate Late-Stage T Effector Differentiation See article p. 1767 A Missing CD8+ Response for a CD8-Dependent Neoepitope See article p. 1783 CD40 TRAF Binding Motifs in Immune Function See article p. 1814
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TLR9 plus STING Agonist Adjuvant Combination Induces Potent Neopeptide T Cell Immunity and Improves Immune Checkpoint Blockade Efficacy in a Tumor Model J. Immunol. (IF 4.4) Pub Date : 2023-12-08 Melisa D. Castro Eiro, Kou Hioki, Ling Li, Merel E. P. Wilmsen, Caoimhe H. Kiernan, Inge Brouwers-Haspels, Marjan van Meurs, Manzhi Zhao, Harm de Wit, Dwin G. B. Grashof, Harmen J. G. van de Werken, Yvonne M. Mueller, Christopher Schliehe, Burcu Temizoz, Kouji Kobiyama, Ken J. Ishii, Peter D. Katsikis
Abstract Immune checkpoint blockade (ICB) immunotherapies have emerged as promising strategies for the treatment of cancer; however, there remains a need to improve their efficacy. Determinants of ICB efficacy are the frequency of tumor mutations, the associated neoantigens, and the T cell response against them. Therefore, it is expected that neoantigen vaccinations that boost the antitumor T cell
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The Teleost CXCL13–CXCR5 Axis Induces Inflammatory Cytokine Expression through the Akt–NF-κB, p38–AP-1, and p38–NF-κB Pathways J. Immunol. (IF 4.4) Pub Date : 2023-12-06 Chunhua Ding, Tiaoyi Xiao, Yadong Deng, Hong Yang, Baohong Xu, Junhua Li, Zhao Lv
Abstract The ancestors of chemokines originate in the most primitive of vertebrates, which has recently attracted great interest in the immune functions and the underlying mechanisms of fish chemokines. In the current study, we identified an evolutionarily conserved chemokine, CiCXCL13, from a teleost fish, grass carp. CiCXCL13 was characterized by a typical SCY (small cytokine CXC) domain and four
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The UAF1–USP1 Deubiquitinase Complex Stabilizes cGAS and Facilitates Antiviral Responses J. Immunol. (IF 4.4) Pub Date : 2023-12-06 Zhongxia Yu, Li Tong, Chenkai Ma, Hui Song, Jie Wang, Li Chai, Caiwei Wang, Mengge Wang, Chunying Wang, Rongzhen Yan, Yue Fu, Mutian Jia, Wei Zhao, Chunyuan Zhao
Abstract Cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) detects cytoplasmic microbial DNA and self-DNA from genomic instability, initiates innate immunity, and plays fundamental roles in defense against viruses and the development of various diseases. The cellular cGAS level determines the magnitude of the response to DNA. However, the underlying mechanisms of the control of
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Mouse Trophoblast Cells Have Attenuated Responses to TNF-α and IFN-γ and Can Avoid Synergic Cytotoxicity of the Two Cytokines J. Immunol. (IF 4.4) Pub Date : 2023-12-06 Mona Fendereski, Hao Ming, Zongliang Jiang, Yan-Lin Guo
Abstract TNF-α and IFN-γ are two inflammatory cytokines that play critical roles in immune responses, but they can also negatively affect cell proliferation and viability. In particular, the combination of the two cytokines (TNF-α/IFN-γ) synergistically causes cytotoxicity in many cell types. We recently reported that mouse embryonic stem cells (ESCs) isolated from the blastocyst stage embryo do not
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Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28− CD8 T Cells in HIV Infection and Atherosclerosis via the CD2–LFA-3 Axis J. Immunol. (IF 4.4) Pub Date : 2023-12-04 Nicole E. Winchester, Soumya Panigrahi, Anokhi Haria, Archeesha Chakraborty, Xi Su, Bonnie Chen, Stephen R. Morris, Brian M. Clagett, Steven M. Juchnowski, Raghavendra Yadavalli, Francois Villinger, Mirko Paiardini, Karem Harth, Vikram S. Kashyap, Leonard H. Calabrese, Leonid Margolis, Scott F. Sieg, Carey L. Shive, Sara Gianella, Nicholas T. Funderburg, David A. Zidar, Michael M. Lederman, Michael
Abstract CD8 T cells are emerging as important mediators in atherosclerosis and cardiovascular disease (CVD). Immune activation may play a particular role in people with HIV (PWH) who are at an increased risk of CVD, even after controlling for known CVD risk factors. Latent CMV infection is associated with increased CVD risk for both PWH and people without HIV, and human CMV-specific CD4 and CD8 T
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Inflammasome Activation and IL-1β Release Triggered by Nanosecond Pulsed Electric Fields in Murine Innate Immune Cells and Skin J. Immunol. (IF 4.4) Pub Date : 2023-12-04 Flavia Mazzarda, Alexandra E. Chittams-Miles, Julia Pittaluga, Esin B. Sözer, P. Thomas Vernier, Claudia Muratori
Abstract Although electric field–induced cell membrane permeabilization (electroporation) is used in a wide range of clinical applications from cancer therapy to cardiac ablation, the cellular- and molecular-level details of the processes that determine the success or failure of these treatments are poorly understood. Nanosecond pulsed electric field (nsPEF)–based tumor therapies are known to have
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Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1 J. Immunol. (IF 4.4) Pub Date : 2023-12-01 Maximilian Nickenig, Matthew S. J. Mangan, Hye Eun Lee, Konstantinos Symeonidis, Antonia Henne, Romina Kaiser, Eike Geißmar, Hendrikus Garritsen, Zeinab Abdullah, Karsten Hiller, Eicke Latz, Mario A. Lauterbach
Abstract The 2′3′-cyclic GMP-AMP (cGAMP) synthase (cGAS)–stimulator of IFN genes (STING) pathway can sense infection and cellular stress by detecting cytosolic DNA. Upon ligand binding, cGAS produces the cyclic dinucleotide messenger cGAMP, which triggers its receptor STING. Active STING initiates gene transcription through the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB and induces
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Antimicrobial Protein LECT2-b Helps Maintain Gut Microbiota Homeostasis via Selectively Targeting Certain Pathogenic Bacteria J. Immunol. (IF 4.4) Pub Date : 2023-12-01 Ya-Zhen Hu, Chang-Song Wu, Jie Wang, Xue-Qing Han, Pei-Yue Si, Yong-An Zhang, Xu-Jie Zhang
Abstract Antimicrobial peptides/proteins (AMPs) constitute a critical component of gut immunity in animals, protecting the gut from pathogenic bacteria. However, the interactions between AMPs and gut microbiota remain elusive. In this study, we show that leukocyte-derived chemotaxin-2 (LECT2)-b, a recently discovered AMP, helps maintain gut homeostasis in grass carp (Ctenopharyngodon idella), one of
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The Microbial Tryptophan Metabolite Contributes to the Remission of Salmonella typhimurium Infection in Mice J. Immunol. (IF 4.4) Pub Date : 2023-11-29 Yingying Li, Junqi Li, Dan Jia, Shandian Gao, Yanan Guo, Junlong Liu, Jinming Wang, Guiquan Guan, Jianxun Luo, Hong Yin, Sa Xiao, Youquan Li
Abstract Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm–infected C57BL6/J mice were used to demonstrate the therapeutic benefits