Article
Immunology
Sarah Sun, Raul Aguirre-Gamboa, Luis B. B. Barreiro
Summary: Trained immunity, characterized by the retention of stimulus-induced histone PTMs, can persist in dividing cells even without direct copying of PTMs during DNA replication. Through experiments, it is found that trained macrophages are reprogrammed in terms of transcription, epigenetics, and function for at least 14 cell divisions after stimulus washout. The long-lasting epigenetic differences between trained and non-trained cells are always associated with changes in transcription factor activity, indicating the central role of TFs and gene expression changes in transmitting stimulus-induced epigenetic changes across cell divisions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Xiaoming Zhang, Laura Kracht, Antonio M. Lerario, Marissa L. Dubbelaar, Nieske Brouwer, Evelyn M. Wesseling, Erik W. G. M. Boddeke, Bart J. L. Eggen, Susanne M. Kooistra
Summary: This study provides insight into epigenetic profiles and transcription factor networks associated with transcriptional signatures of tolerized and trained microglia in vivo, leading to a better understanding of innate immune memory of microglia.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Immunology
Giacomo Della Camera, Mariusz Madej, Anna Maria Ferretti, Rita La Spina, Yang Li, Annunziata Corteggio, Tommaso Heinzl, Benjamin J. Swartzwelter, Gergo Sipos, Sabrina Gioria, Alessandro Ponti, Diana Boraschi, Paola Italiani
Summary: This study found that nanoparticles used for diagnostic imaging, such as gold and iron oxide nanoparticles, can induce or modulate innate memory in human primary monocytes. The effects on innate memory were found to be donor-dependent, suggesting personalized profiling would be needed to predict the impact of imaging nanoparticles on patients' innate immune reactivity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Siroon Bekkering, Jorge Dominguez-Andres, Leo A. B. Joosten, Niels P. Riksen, Mihai G. Netea
Summary: Trained immunity is a newly recognized phenomenon where cells of the innate immune system exhibit memory characteristics and enhanced responses upon secondary challenge. It explains the heterologous effects of vaccines, but can also lead to maladaptive effects in chronic inflammatory conditions.
ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
(2021)
Review
Immunology
Michelle Felicia Lee, Guan Zhong Voon, Hui Xuan Lim, Mun Lok Chua, Chit Laa Poh
Summary: Dengue is a mosquito-borne disease that poses significant public health concerns in tropical and subtropical countries. The dengue virus has evolved various strategies to manipulate the host's immune responses, and miRNAs and DENV non-structural proteins (NS) are promising targets for anti-dengue therapeutics.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Iwona T. Myszor, Gudmundur Hrafn Gudmundsson
Summary: The innate immune system of the airway epithelium consists of multiple components that work together to protect the host from invading pathogens. Modulating innate immune responses in the airway epithelium to boost host defenses and enhance immune responses is an alternative approach to standard antibiotics. This review discusses the possibilities of such modulation for host-directed therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Kavita Rawat, Shannon M. Soucy, Fred W. Kolling, Kiara Manohar Diaz, William T. King, Anita Tewari, Claudia V. Jakubzick
Summary: Recent studies have revealed the critical role of natural antibodies (NAbs) in antitumor immune responses. However, the role of NAbs in cancer immunosurveillance has not been explored due to the lack of in vivo models. In this article, the authors propose a role for NAbs in alerting the immune system against precancerous neoantigen-expressing cells. Four reproducible neoantigen-expressing cell models are identified, allowing investigation of cancer immunosurveillance mediators. The presence of NAbs is essential for the elimination of transformed cells and immunity against neoantigens. Additionally, NAb-deficient mice show a greater tumor burden in chemically and virally induced tumor models. Restoration of NAb repertoire leads to the recognition and elimination of neoantigen-expressing cells and cancer.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Neurosciences
Ricardo Martins-Ferreira, Barbara Leal, Paulo Pinho Costa, Esteban Ballestar
Summary: Microglia play a crucial role in the immune defense of the central nervous system, with high phenotypic plasticity and involvement in neurological pathologies. The concept of innate immune memory and epigenetic reprogramming are closely linked to microglial activation and response in CNS diseases.
PROGRESS IN NEUROBIOLOGY
(2021)
Review
Cell Biology
Arailym Aronova, Federica Tosato, Nawraa Naser, Yaw Asare
Summary: Innate immune pathways play a crucial role in the development of atherosclerosis and targeting these pathways may effectively reduce the risk of cardiovascular disease. Understanding the interplay between these pathways and the long-term reprogramming of immune cells is essential for the development of targeted therapeutic interventions.
Review
Immunology
Qian Zhang, Xuetao Cao
Summary: The innate immune response is a rapid and precise reaction to pathogens, aiming to efficiently eliminate them while avoiding excessive inflammation. The epiregulome, shaped by epigenetic factors, gives innate immune cells specialized phenotypes and functions, contributing to the resolution of inflammatory responses.
ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
(2021)
Review
Immunology
Shasha Chen, Zhiyong Liao, Pinglong Xu
Summary: Mitochondria play versatile roles in cellular processes and have emerged as critical components in innate immunity. This review provides a comprehensive exploration of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. It discusses the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling via mitophagy. Additionally, it explores the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, immune cell polarization, and their implications in infectious and inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Feng-Ming Tien, Hsuan-Hsuan Lu, Shu-Yung Lin, Hsing-Chen Tsai
Summary: The tumor immune microenvironment is a complex system where immune cell subtypes interact with cancer cells and stromal cells. The composition and characteristics of the immune landscape during cancer development greatly impact the effectiveness of systemic antitumor therapy in patients. Epigenetic mechanisms play a key role in antitumor immunity and immune state transitions. Targeting epigenetic modifiers to reshape the immune microenvironment has the potential to improve cancer immunotherapy and overcome therapeutic challenges.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Review
Fisheries
Wei Yang, Ngoc Tuan Tran, Chun-Hua Zhu, De-Fu Yao, Jude Juventus Aweya, Yi Gong, Hong-Yu Ma, Yue-Ling Zhang, Guang-Li Li, Sheng-Kang Li
Summary: Immune priming has been demonstrated as a form of immune memory in invertebrates without acquired immune systems, with implications for vaccinating economically valuable shellfish. Research on priming responses and mechanisms is necessary for the development of prophylactic strategies. Both humoral and cellular factors are involved in priming protection, but cellular immunity appears to be more important in pathogen clearance and survival.
Review
Biochemistry & Molecular Biology
Yuanchun Xu, Zongsheng He, Jing Du, Ziqiang Chen, John W. M. Creemers, Bin Wang, Fan Li, Yaling Wang
Summary: The dysfunction of immune cell development, often caused by aberrations in epigenetic regulators, is closely related to immunological homeostasis and various human diseases. Understanding the role of epigenetic modulations in immune cell development can lead to the identification of new strategies for disease treatment. This article reviews recent advances in this field, highlighting the impact of epigenetic regulators on gene expression and their implications in tumor progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Medicine, Research & Experimental
Xiaoqiang Gao, Shi Zuo
Summary: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its cases are increasing. The treatment of advanced HCC is challenging, but immune checkpoint inhibitor therapy has been a significant breakthrough. A combination therapy of Atezolizumab and bevacizumab has been approved as a first-line treatment for advanced HCC, although its effectiveness is limited. Understanding the tumor immune microenvironment and current immunotherapeutic approaches is crucial.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Nicholas M. Adams, Carlos Diaz-Salazar, Celeste Dang, Lewis L. Lanier, Joseph C. Sun
Summary: This study indicates that there are differences in homeostatic turnover dynamics between tissue-resident ILC1s and circulating NK cells, with NK cell turnover accelerated in the absence of the transcription factor Eomes. Furthermore, NK cell age heterogeneity diversifies their function, with older NK cells showing greater IFN-gamma production and robust adaptive responses during CMV infection.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Sam Sheppard, Joseph C. Sun
Summary: NK cells express a limited number of germline-encoded receptors that identify infected or transformed cells, eliciting cytotoxicity, effector cytokine production, and in some circumstances clonal proliferation and memory. Cytomegalovirus infection in both species can expand a population of NK cells expressing receptors critical to the clearance of infected cells and generate a long-lived memory pool capable of targeting future infection with greater efficacy.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yuri Pritykin, Joris van der Veeken, Allison R. Pine, Yi Zhong, Merve Sahin, Linas Mazutis, Dana Pe'er, Alexander Y. Rudensky, Christina S. Leslie
Summary: CD8 T cells are crucial in defending against viral and bacterial infections as well as tumor immunity, but their loss of functionality is complex due to the heterogeneity of states described in experimental and clinical settings. By analyzing a unified dataset of over 300 experiments, a shared trajectory of differentiation towards dysfunction was defined, revealing an early bifurcation of functional and dysfunctional T cell states across models. Experimental dissection of acute and chronic viral infections identified state-specific drivers and progenitor-like populations at an early branch point, aiding in mechanistic studies and translational efforts.
Biographical-Item
Immunology
Gianna E. Hammer, Susan R. Schwab, Joseph C. Sun
Article
Immunology
Gabriela M. Wiedemann, Endi K. Santosa, Simon Grassmann, Sam Sheppard, Jean-Benoit Le Luduec, Nicholas M. Adams, Celeste Dang, Katharine C. Hsu, Joseph C. Sun, Colleen M. Lau
Summary: Research demonstrates that the antiviral responses of NK cells are influenced by cytokine signaling through STAT proteins, with proinflammatory and homeostatic cytokines forming a cooperative axis to regulate global gene expression and affect NK cell activity through diverse modes of epigenetic regulation.
Article
Cell Biology
Minggang Zhang, Zeguo Zhao, Yuri Pritykin, Margaret Hannum, Andrew C. Scott, Fengshen Kuo, Viraj Sanghvi, Timothy A. Chan, Venkatraman Seshan, Hans-Guido Wendel, Andrea Schietinger, Michel Sadelain, Morgan Huse
Summary: The study showed that ectopic expression of miR-200c enhanced the antitumor activity of CD8(+) cytotoxic T lymphocytes during adoptive T cell therapy (ACT) in mouse models, leading to reduced apoptosis, increased in vivo persistence, and up-regulation of certain genes. These genetic perturbations resulted in phenotypically distinct T cells with advantageous therapeutic properties, highlighting the potential of the miR-200c-EpCAM axis in improving ACT outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Jue Feng, Joseph N. Pucella, Geunhyo Jang, Marcela Alcantara-Hernandez, Samik Upadhaya, Nicholas M. Adams, Alireza Khodadadi-Jamayran, Colleen M. Lau, Marlon Stoeckius, Stephanie Hao, Peter Smibert, Aristotelis Tsirigos, Juliana Idoyaga, Boris Reizis
Summary: This study investigates the developmental origins of dendritic cells (DCs) and reveals the shared origin of pDCs and cDCs, suggesting a revised scheme of DC development.
Review
Immunology
Colleen M. Lau, Gabriela M. Wiedemann, Joseph C. Sun
Summary: Immunological memory refers to the mechanism by which the immune system produces an enhanced secondary response upon re-encounter with pathogens. Recent evidence challenges the notion that memory responses are restricted to the adaptive immune system, with NK cells of the innate immune system also playing a crucial role. NK cells, like T cells, require multiple signals for optimal responses.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Yi Zhong, Sarah K. Walker, Yuri Pritykin, Christina S. Leslie, Alexander Y. Rudensky, Joris van der Veeken
Summary: Zhong et al. studied the transcriptional regulation of T cell gene expression upon viral challenge using B6/Cast F1 hybrid mice. They found that members of Ets, Runx, and TCF/Lef transcription factor families play key roles in maintaining or increasing chromatin accessibility during T cell activation. Some highly induced immune response genes exhibit a noncanonical TF recruitment pattern.
Article
Immunology
Joris van der Veeken, Clarissa Campbell, Yuri Pritykin, Michail Schizas, Jacob Verter, Wei Hu, Zhong-Min Wang, Fanny Matheis, Daniel Mucida, Louis-Marie Charbonnier, Talal A. Chatila, Alexander Y. Rudensky
Summary: The role of Foxp3 in peripheral pTreg cells and the mechanisms supporting their differentiation remain poorly understood. This study used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. While Foxp3 was critical for the suppression of certain diseases, pTreg cells could suppress colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals preceding and promoting its expression confer distinct facets of pTreg functionality.
Editorial Material
Immunology
Simon Grassmann, Joseph C. Sun
Summary: New technologies are being used to investigate clonal expansion and immunological memory of human natural killer cells during human cytomegalovirus infection. These processes provide protective immunity against repeated pathogen exposure.
Article
Multidisciplinary Sciences
Geunhyo Jang, Stephania Contreras Castillo, Eduardo Esteva, Samik Upadhaya, Jue Feng, Nicholas M. Adams, Elodie Richard, Rajeshwar Awatramani, Catherine M. Sawai, Boris Reizis
Summary: Mammalian aging is associated with defects in hematopoiesis, particularly in the development of T and B lymphocytes. This impairment is believed to be caused by the accumulation of hematopoietic stem cells (HSCs) with myeloid bias in the bone marrow. However, research using genetic labeling and tracing techniques showed that the HSC population in old mice had reduced differentiation into all lineages, including lymphoid cells. The partial decoupling of old HSCs from hematopoiesis, rather than myeloid bias, was found to be the primary cause of the selective impairment of lymphopoiesis in older mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Endi K. Santosa, Joseph C. Sun
Summary: This review draws parallels from T cell biology to explore the key features of immune memory in innate lymphocytes. It discusses the quantity, quality, and location of innate lymphocytes, as well as the signals and mechanisms involved in their clonal expansion and differentiation toward a memory fate. The review also highlights the possibility of activated innate lymphocytes relocating to specific peripheral tissues during infection, similar to tissue-resident memory T cells.
Article
Immunology
Fernando Bandeira Sulczewski, Raul A. Maqueda-Alfaro, Marcela Alcantara-Hernandez, Oriana A. Perez, Sanjana Saravanan, Tae Jin Yun, David Seong, Rebeca Arroyo Hornero, Hayley M. Raquer-McKay, Eduardo Esteva, Zachary R. Lanzar, Rebecca A. Leylek, Nicholas M. Adams, Annesa Das, Adeeb H. Rahman, Andres Gottfried-Blackmore, Boris Reizis, Juliana Idoyaga
Summary: This study investigates the role of transitional dendritic cells (tDCs) in antiviral immune responses and reveals their distinct features compared to other dendritic cell subsets. The authors show that tDCs share bone marrow progenitors with plasmacytoid DCs (pDCs) and contribute to the development of ESAM(+) type 2 DCs (DC2s). Unlike other DC subsets, tDCs exhibit characteristics of differentiated DCs, including antigen capture, response to stimuli, and activation of antigen-specific naive T cells. Moreover, viral sensing by tDCs leads to IL-1β secretion and fatal immune pathology. Overall, tDCs are a unique pDC-related subset with a DC2 differentiation potential and a special proinflammatory function during viral infections.
