E O Serebrovskaya, E A Bryushkova, D K Lukyanov, N V Mushenkova, D M Chudakov, M A Turchaninova
Our current understanding of whether B cell involvement in the tumor microenvironment benefits the patient or the tumor - in distinct cancers, subcohorts and individual patients - is quite limited. Both statements are probably true in most cases: certain clonal B cell populations contribute to the antitumor response, while others steer the immune response away from the desired mechanics. To step up to a new level of understanding and managing B cell behaviors in the tumor microenvironment, we need to rationally discern these roles, which are cumulatively defined by B cell clonal functional programs, specificities of their B cell receptors, specificities and isotypes of the antibodies they produce, and their spatial interactions within the tumor environment...
January 31, 2024: Seminars in Immunology
Evangelos Andreakos
Type I and type III interferons (IFNs) constitute a key antiviral defense systems of the body, inducing viral resistance to cells and mediating diverse innate and adaptive immune functions. Defective type I and type III IFN responses have recently emerged as the 'Achilles heel' in COVID-19, with such patients developing severe disease and exhibiting a high risk for critical pneumonia and death. Here, we review the biology of type I and type III IFNs, their similarities and important functional differences, and their roles in SARS-CoV-2 infection...
January 24, 2024: Seminars in Immunology
Zhaoyu Lin, Qianyue Chen, Hai-Bin Ruan
Intestinal homeostasis is achieved by the balance among intestinal epithelium, immune cells, and gut microbiota. Gasdermins (GSDMs), a family of membrane pore forming proteins, can trigger rapid inflammatory cell death in the gut, mainly pyroptosis and NETosis. Importantly, there is increasing literature on the non-cell lytic roles of GSDMs in intestinal homeostasis and disease. While GSDMA is low and PJVK is not expressed in the gut, high GSDMB and GSDMC expression is found almost restrictively in intestinal epithelial cells...
January 16, 2024: Seminars in Immunology
Susana G Rodrigues, Schalk van der Merwe, Aleksander Krag, Reiner Wiest
No abstract text is available yet for this article.
January 13, 2024: Seminars in Immunology
Christine Moussion, Lélia Delamarre
Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in shaping adaptive immunity. DCs have a unique ability to sample their environment, capture and process exogenous antigens into peptides that are then loaded onto major histocompatibility complex class I molecules for presentation to CD8+ T cells. This process, called cross-presentation, is essential for initiating and regulating CD8+ T cell responses against tumors and intracellular pathogens. In this review, we will discuss the role of DCs in cancer immunity, the molecular mechanisms underlying antigen cross-presentation by DCs, the immunosuppressive factors that limit the efficiency of this process in cancer, and approaches to overcome DC dysfunction and therapeutically promote antitumoral immunity...
November 28, 2023: Seminars in Immunology
Peter van Endert
No abstract text is available yet for this article.
November 7, 2023: Seminars in Immunology
Léonie Dejas, Karin Santoni, Etienne Meunier, Mohamed Lamkanfi
Neutrophils are among the most abundant immune cells, representing about 50%- 70% of all circulating leukocytes in humans. Neutrophils rapidly infiltrate inflamed tissues and play an essential role in host defense against infections. They exert microbicidal activity through a variety of specialized effector mechanisms, including phagocytosis, production of reactive oxygen species, degranulation and release of secretory vesicles containing broad-spectrum antimicrobial factors. In addition to their homeostatic turnover by apoptosis, recent studies have revealed the mechanisms by which neutrophils undergo various forms of regulated cell death...
November 6, 2023: Seminars in Immunology
Mehdi Benamar, Qian Chen, Monica Martinez-Blanco, Talal A Chatila
Regulatory T (Treg) cells maintain immune tolerance to allergens at the environmental interfaces in the airways, skin and gut, marshalling in the process distinct immune regulatory circuits operative in the respective tissues. Treg cells are coordinately mobilized with allergic effector mechanisms in the context of a tissue-protective allergic inflammatory response against parasites, toxins and potentially harmful allergens, serving to both limit the inflammation and promote local tissue repair. Allergic diseases are associated with subverted Treg cell responses whereby a chronic allergic inflammatory environment can skew Treg cells toward pathogenic phenotypes that both perpetuate and aggravate disease...
October 12, 2023: Seminars in Immunology
Bowen Zhou, Derek W Abbott
The gasdermin family of proteins are central effectors of the inflammatory, lytic cell death modality known as pyroptosis. Characterized in 2015, the most well-studied member gasdermin D can be proteolyzed, typically by caspases, to generate an active pore-forming N-terminal domain. At least well-studied three pharmacological inhibitors (necrosulfonamide, disulfiram, dimethyl fumarate) since 2018 have been shown to affect gasdermin D activity either through modulation of processing or interference with pore formation...
October 6, 2023: Seminars in Immunology
Duygu Yazici, Ismail Ogulur, Yagiz Pat, Huseyn Babayev, Elena Barletta, Sena Ardicli, Manal Bel Imam, Mengting Huang, Jana Koch, Manru Li, Debbie Maurer, Urszula Radzikowska, Pattraporn Satitsuksanoa, Stephan R Schneider, Na Sun, Stephan Traidl, Alexandra Wallimann, Sebastian Wawrocki, Damir Zhakparov, Danielle Fehr, Reihane Ziadlou, Yasutaka Mitamura, Marie-Charlotte Brüggen, Willem van de Veen, Milena Sokolowska, Katja Baerenfaller, Kari Nadeau, Mubeccel Akdis, Cezmi A Akdis
Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli...
October 4, 2023: Seminars in Immunology
Junru Wu, Jingjing Cai, Yiting Tang, Ben Lu
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...
September 29, 2023: Seminars in Immunology
Jörg J Goronzy, Nan-Ping Weng
No abstract text is available yet for this article.
September 28, 2023: Seminars in Immunology
Julia Han Noll, Bruce L Levine, Carl H June, Joseph A Fraietta
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...
September 18, 2023: Seminars in Immunology
Djamel Nehar-Belaid, Mark Sokolowski, Sathyabaarathi Ravichandran, Jacques Banchereau, Damien Chaussabel, Duygu Ucar
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...
September 15, 2023: Seminars in Immunology
Rob J de Boer, Kiki Tesselaar, José A M Borghans
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...
September 14, 2023: Seminars in Immunology
A Elisabeth Gressler, Houfu Leng, Heidi Zinecker, Anna Katharina Simon
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...
September 12, 2023: Seminars in Immunology
Cristhian Cadena, Opher S Kornfeld, Bettina L Lee, Nobuhiko Kayagaki
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 [1,2]. 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...
September 11, 2023: Seminars in Immunology
Yanyan Zheng, Qingxiang Liu, Jorg J Goronzy, Cornelia M Weyand
Evidence is emerging that the process of immune aging is a mechanism leading to autoimmunity. Over lifetime, the immune system adapts to profound changes in hematopoiesis and lymphogenesis, and progressively restructures in face of an ever-expanding exposome. Older adults fail to generate adequate immune responses against microbial infections and tumors, but accumulate aged T cells, B cells and myeloid cells. Age-associated B cells are highly efficient in autoantibody production. T-cell aging promotes the accrual of end-differentiated effector T cells with potent cytotoxic and pro-inflammatory abilities and myeloid cell aging supports a low grade, sterile and chronic inflammatory state (inflammaging)...
September 2023: Seminars in Immunology
Timur O Yarovinsky, Meiling Su, Chaofei Chen, Yaozu Xiang, Wai Ho Tang, John Hwa
Pyroptosis is a form of programmed cell death associated with activation of inflammasomes and inflammatory caspases, proteolytic cleavage of gasdermin proteins (forming pores in the plasma membrane), and selective release of proinflammatory mediators. Induction of pyroptosis results in amplification of inflammation, contributing to the pathogenesis of chronic cardiovascular diseases such as atherosclerosis and diabetic cardiomyopathy, and acute cardiovascular events, such as thrombosis and myocardial infarction...
September 2023: Seminars in Immunology
Sara Carloni, Maria Rescigno
The multifaceted microbiota characterizing our gut plays a crucial role in maintaining immune, metabolic and tissue homeostasis of the intestine as well as of distal organs, including the central nervous system. Microbial dysbiosis is reported in several inflammatory intestinal diseases characterized by the impairment of the gut epithelial and vascular barriers, defined as leaky gut, and it is reported as a potential danger condition associated with the development of metabolic, inflammatory and neurodegenerative diseases...
September 2023: Seminars in Immunology
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