{"title":"The noncanonical inflammasome-induced pyroptosis and septic shock","authors":"Junru Wu , Jingjing Cai , Yiting Tang , Ben Lu","doi":"10.1016/j.smim.2023.101844","DOIUrl":"10.1016/j.smim.2023.101844","url":null,"abstract":"<div><p>Sepsis remains one of the most common and lethal conditions globally. Currently, no proposed target specific to sepsis improves survival in clinical trials. Thus, an in-depth understanding of the pathogenesis of sepsis is needed to propel the discovery of effective treatment. Recently attention to sepsis has intensified because of a growing recognition of a non-canonical inflammasome-triggered lytic mode of cell death termed pyroptosis upon sensing cytosolic lipopolysaccharide (LPS). Although the consequences of activation of the canonical and non-canonical inflammasome are similar, the non-canonical inflammasome formation requires caspase-4/5/11, which enzymatically cleave the pore-forming protein gasdermin D (GSDMD) and thereby cause pyroptosis. The non-canonical inflammasome assembly triggers such inflammatory cell death by itself; or leverages a secondary activation of the canonical NLRP3 inflammasome pathway. Excessive cell death induced by oligomerization of GSDMD and NINJ1 leads to cytokine release and massive tissue damage, facilitating devastating consequences and death. This review summarized the updated mechanisms that initiate and regulate non-canonical inflammasome activation and pyroptosis and highlighted various endogenous or synthetic molecules as potential therapeutic targets for treating sepsis.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101844"},"PeriodicalIF":7.8,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The immunology and cell biology of T cell aging","authors":"Jörg J. Goronzy, Nan-ping Weng","doi":"10.1016/j.smim.2023.101843","DOIUrl":"10.1016/j.smim.2023.101843","url":null,"abstract":"","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101843"},"PeriodicalIF":7.8,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia Han Noll , Bruce L. Levine , Carl H. June , Joseph A. Fraietta
{"title":"Beyond youth: Understanding CAR T cell fitness in the context of immunological aging","authors":"Julia Han Noll , Bruce L. Levine , Carl H. June , Joseph A. Fraietta","doi":"10.1016/j.smim.2023.101840","DOIUrl":"10.1016/j.smim.2023.101840","url":null,"abstract":"<div><p>Population aging, a pervasive global demographic trend, is anticipated to challenge health and social systems worldwide. This phenomenon is due to medical advancements enabling longer lifespans, with 20% of the US population soon to be over 65 years old. Consequently, there will be a surge in age-related diseases. Senescence, characterized by the loss of biological maintenance and homeostasis at molecular and cellular levels, either correlates with or directly causes age-related phenotypic changes. Decline of the immune system is a critical factor in the senescence process, with cancer being a primary cause of death in elderly populations. Chimeric antigen receptor (CAR) T cell therapy, an innovative approach, has demonstrated success mainly in pediatric and young adult hematological malignancies but remains largely ineffective for diseases affecting older populations, such as late-in-life B cell malignancies and most solid tumor indications. This limitation arises because CAR T cell efficacy heavily relies on the fitness of the patient-derived starting T cell material. Numerous studies suggest that T cell senescence may be a key driver of CAR T cell deficiency. This review examines correlates and underlying factors associated with favorable CAR T cell outcomes and explores potential experimental and clinically actionable strategies for T cell rejuvenation.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101840"},"PeriodicalIF":7.8,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Djamel Nehar-Belaid , Mark Sokolowski , Sathyabaarathi Ravichandran , Jacques Banchereau , Damien Chaussabel , Duygu Ucar
{"title":"Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS","authors":"Djamel Nehar-Belaid , Mark Sokolowski , Sathyabaarathi Ravichandran , Jacques Banchereau , Damien Chaussabel , Duygu Ucar","doi":"10.1016/j.smim.2023.101842","DOIUrl":"10.1016/j.smim.2023.101842","url":null,"abstract":"<div><p>Vaccines are among the greatest inventions in medicine, leading to the elimination or control of numerous diseases, including smallpox, polio, measles, rubella, and, most recently, COVID-19. Yet, the effectiveness of vaccines varies among individuals. In fact, while some recipients mount a robust response to vaccination that protects them from the disease, others fail to respond. Multiple clinical and epidemiological factors contribute to this heterogeneity in responsiveness. Systems immunology studies fueled by advances in single-cell biology have been instrumental in uncovering pre-vaccination immune cell types and genomic features (i.e., the baseline immune state, BIS) that have been associated with vaccine responsiveness. Here, we review clinical factors that shape the BIS, and the characteristics of the BIS associated with responsiveness to frequently studied vaccines (i.e., influenza, COVID-19, bacterial pneumonia, malaria). Finally, we discuss potential strategies to enhance vaccine responsiveness in high-risk groups, focusing specifically on older adults.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101842"},"PeriodicalIF":7.8,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rob J. de Boer , Kiki Tesselaar , José A.M. Borghans
{"title":"Better safe than sorry: Naive T-cell dynamics in healthy ageing","authors":"Rob J. de Boer , Kiki Tesselaar , José A.M. Borghans","doi":"10.1016/j.smim.2023.101839","DOIUrl":"10.1016/j.smim.2023.101839","url":null,"abstract":"<div><p>It is well-known that the functioning of the immune system gradually deteriorates with age, and we are increasingly confronted with its consequences as the life expectancy of the human population increases. Changes in the T-cell pool are among the most prominent features of the changing immune system during healthy ageing, and changes in the naive T-cell pool in particular are generally held responsible for its gradual deterioration. These changes in the naive T-cell pool are thought to be due to involution of the thymus. It is commonly believed that the gradual loss of thymic output induces compensatory mechanisms to maintain the number of naive T cells at a relatively constant level, and induces a loss of diversity in the T-cell repertoire. Here we review the studies that support or challenge this widely-held view of immune ageing and discuss the implications for vaccination strategies.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101839"},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Elisabeth Gressler , Houfu Leng , Heidi Zinecker , Anna Katharina Simon
{"title":"Proteostasis in T cell aging","authors":"A. Elisabeth Gressler , Houfu Leng , Heidi Zinecker , Anna Katharina Simon","doi":"10.1016/j.smim.2023.101838","DOIUrl":"10.1016/j.smim.2023.101838","url":null,"abstract":"<div><p>Aging leads to a decline in immune cell function, which leaves the organism vulnerable to infections and age-related multimorbidities. One major player of the adaptive immune response are T cells, and recent studies argue for a major role of disturbed proteostasis contributing to reduced function of these cells upon aging. Proteostasis refers to the state of a healthy, balanced proteome in the cell and is influenced by synthesis (translation), maintenance and quality control of proteins, as well as degradation of damaged or unwanted proteins by the proteasome, autophagy, lysosome and cytoplasmic enzymes. This review focuses on molecular processes impacting on proteostasis in T cells, and specifically functional or quantitative changes of each of these upon aging. Importantly, we describe the biological consequences of compromised proteostasis in T cells, which range from impaired T cell activation and function to enhancement of inflamm-aging by aged T cells. Finally, approaches to improve proteostasis and thus rejuvenate aged T cells through pharmacological or physical interventions are discussed.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101838"},"PeriodicalIF":7.8,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10244057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristhian Cadena, Opher S. Kornfeld, Bettina L. Lee, Nobuhiko Kayagaki
{"title":"Epigenetic and transcriptional control of gasdermins","authors":"Cristhian Cadena, Opher S. Kornfeld, Bettina L. Lee, Nobuhiko Kayagaki","doi":"10.1016/j.smim.2023.101841","DOIUrl":"10.1016/j.smim.2023.101841","url":null,"abstract":"<div><p>Cells undergo an inflammatory programmed lytic cell death called ‘pyroptosis’ (with the Greek roots ‘fiery’), often featuring morphological hallmarks such as large ballooning protrusions and subsequent bursting. Originally described as a caspase-1-dependent cell death in response to bacterial infection, pyroptosis has since been re-defined in 2018 as a cell death dependent on plasma membrane pores by a gasdermin (GSDM) family member <span>[1]</span>, <span>[2]</span>. GSDMs form pores in the plasma membrane as well as organelle membranes, thereby initiating membrane destruction and the rapid and lytic demise of a cell. The gasdermin family plays a profound role in the execution of pyroptosis in the context of infection, inflammation, tumor pathogenesis, and anti-tumor therapy. More recently, cell-death-independent functions for some of the GSDMs have been proposed. Therefore, a comprehensive understanding of gasdermin gene regulation, including mechanisms in both homeostatic conditions and during inflammation, is essential. In this review, we will summarize the role of gasdermins in pyroptosis and focus our discussion on the transcriptional and epigenetic mechanisms controlling the expression of GSDMs.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101841"},"PeriodicalIF":7.8,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10597273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammasomes as regulators of non-infectious disease","authors":"Daniel Okin , Jonathan C. Kagan","doi":"10.1016/j.smim.2023.101815","DOIUrl":"10.1016/j.smim.2023.101815","url":null,"abstract":"<div><p>Inflammasomes are cytoplasmic organelles that stimulate inflammation upon cellular detection of infectious or non-infectious stress. While much foundational work has focused on the infection-associated aspects of inflammasome activities, recent studies have highlighted the role of inflammasomes in non-infectious cellular and organismal functions. Herein, we discuss the evolution of inflammasome components and highlight characteristics that permit inflammasome regulation of physiologic processes. We focus on emerging data that highlight the importance of inflammasome proteins in the regulation of reproduction, development, and malignancy. A framework is proposed to contextualize these findings.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101815"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging","authors":"Ayako Kurioka , Paul Klenerman","doi":"10.1016/j.smim.2023.101816","DOIUrl":"10.1016/j.smim.2023.101816","url":null,"abstract":"<div><p>Unconventional T cells include γδ T cells, invariant Natural Killer T cells (iNKT) cells and Mucosal Associated Invariant T (MAIT) cells, which are distinguished from conventional T cells by their recognition of non-peptide ligands presented by non-polymorphic antigen presenting molecules and rapid effector functions that are pre-programmed during their development. Here we review current knowledge of the effect of age on unconventional T cells, from early life to old age, in both mice and humans. We then discuss the role of unconventional T cells in age-associated diseases and infections, highlighting the similarities between members of the unconventional T cell family in the context of aging.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101816"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introduction to the Special Issue: The Immunopeptidome","authors":"Étienne Caron, Claude Perreault","doi":"10.1016/j.smim.2023.101798","DOIUrl":"10.1016/j.smim.2023.101798","url":null,"abstract":"","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101798"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10165297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}