Seminars in Immunopathology最新文献

{"title":"The role of circulating cell-free DNA as an inflammatory mediator after stroke.","authors":"Stefan Roth,&nbsp;Saskia R Wernsdorf,&nbsp;Arthur Liesz","doi":"10.1007/s00281-023-00993-5","DOIUrl":"https://doi.org/10.1007/s00281-023-00993-5","url":null,"abstract":"<p><p>Stroke is the second leading cause of death worldwide and a leading cause of disability. Clinical and experimental studies highlighted the complex role of the immune system in the pathophysiology of stroke. Ischemic brain injury leads to the release of cell-free DNA, a damage-associated molecular pattern, which binds to pattern recognition receptors on immune cells such as toll-like receptors and cytosolic inflammasome sensors. The downstream signaling cascade then induces a rapid inflammatory response. In this review, we are highlighting the characteristics of cell-free DNA and how these can affect a local as well as a systemic response after stroke. For this purpose, we screened literature on clinical studies investigating cell-free DNA concentration and properties after brain ischemia. We report the current understanding for mechanisms of DNA uptake and sensing in the context of post-stroke inflammation. Moreover, we compare possible treatment options targeting cell-free DNA, DNA-sensing pathways, and the downstream mediators. Finally, we describe clinical implications of this inflammatory pathway for stroke patients, open questions, and potential future research directions.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"411-425"},"PeriodicalIF":9.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707309","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":"Immune compartments at the brain's borders in health and neurovascular diseases.","authors":"Jennifer E Goertz, Lidia Garcia-Bonilla, Costantino Iadecola, Josef Anrather","doi":"10.1007/s00281-023-00992-6","DOIUrl":"10.1007/s00281-023-00992-6","url":null,"abstract":"<p><p>Recent evidence implicates cranial border immune compartments in the meninges, choroid plexus, circumventricular organs, and skull bone marrow in several neuroinflammatory and neoplastic diseases. Their pathogenic importance has also been described for cardiovascular diseases such as hypertension and stroke. In this review, we will examine the cellular composition of these cranial border immune niches, the potential pathways through which they might interact, and the evidence linking them to cardiovascular disease.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"437-449"},"PeriodicalIF":7.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143227","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":"Systemic innate myeloid responses to acute ischaemic and haemorrhagic stroke.","authors":"Ruth Stephens,&nbsp;John R Grainger,&nbsp;Craig J Smith,&nbsp;Stuart M Allan","doi":"10.1007/s00281-022-00968-y","DOIUrl":"10.1007/s00281-022-00968-y","url":null,"abstract":"<p><p>Acute ischaemic and haemorrhagic stroke account for significant disability and morbidity burdens worldwide. The myeloid arm of the peripheral innate immune system is critical in the immunological response to acute ischaemic and haemorrhagic stroke. Neutrophils, monocytes, and dendritic cells (DC) contribute to the evolution of pathogenic local and systemic inflammation, whilst maintaining a critical role in ongoing immunity protecting against secondary infections. This review aims to summarise the key alterations to myeloid immunity in acute ischaemic stroke, intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH). By integrating clinical and preclinical research, we discover how myeloid immunity is affected across multiple organ systems including the brain, blood, bone marrow, spleen, and lung, and evaluate how these perturbations associate with real-world outcomes including infection. These findings are placed in the context of the rapidly developing field of human immunology, which offers a wealth of opportunity for further research.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"281-294"},"PeriodicalIF":9.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689595","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":"Role of glia and extracellular matrix in controlling neuroplasticity in the central nervous system.","authors":"Egor Dzyubenko,&nbsp;Dirk M Hermann","doi":"10.1007/s00281-023-00989-1","DOIUrl":"https://doi.org/10.1007/s00281-023-00989-1","url":null,"abstract":"<p><p>Neuronal plasticity is critical for the maintenance and modulation of brain activity. Emerging evidence indicates that glial cells actively shape neuroplasticity, allowing for highly flexible regulation of synaptic transmission, neuronal excitability, and network synchronization. Astrocytes regulate synaptogenesis, stabilize synaptic connectivity, and preserve the balance between excitation and inhibition in neuronal networks. Microglia, the brain-resident immune cells, continuously monitor and sculpt synapses, allowing for the remodeling of brain circuits. Glia-mediated neuroplasticity is driven by neuronal activity, controlled by a plethora of feedback signaling mechanisms and crucially involves extracellular matrix remodeling in the central nervous system. This review summarizes the key findings considering neurotransmission regulation and metabolic support by astrocyte-neuronal networks, and synaptic remodeling mediated by microglia. Novel data indicate that astrocytes and microglia are pivotal for controlling brain function, indicating the necessity to rethink neurocentric neuroplasticity views.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"377-387"},"PeriodicalIF":9.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697392","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":"The role of the ATP-adenosine axis in ischemic stroke.","authors":"Ines Sophie Schädlich,&nbsp;Riekje Winzer,&nbsp;Joschi Stabernack,&nbsp;Eva Tolosa,&nbsp;Tim Magnus,&nbsp;Björn Rissiek","doi":"10.1007/s00281-023-00987-3","DOIUrl":"https://doi.org/10.1007/s00281-023-00987-3","url":null,"abstract":"<p><p>In ischemic stroke, the primary neuronal injury caused by the disruption of energy supply is further exacerbated by secondary sterile inflammation. The inflammatory cascade is largely initiated by the purine adenosine triphosphate (ATP) which is extensively released to the interstitial space during brain ischemia and functions as an extracellular danger signaling molecule. By engaging P2 receptors, extracellular ATP activates microglia leading to cytokine and chemokine production and subsequent immune cell recruitment from the periphery which further amplifies post-stroke inflammation. The ectonucleotidases CD39 and CD73 shape and balance the inflammatory environment by stepwise degrading extracellular ATP to adenosine which itself has neuroprotective and anti-inflammatory signaling properties. The neuroprotective effects of adenosine are mainly mediated through A₁ receptors and inhibition of glutamatergic excitotoxicity, while the anti-inflammatory capacities of adenosine have been primarily attributed to A_2A receptor activation on infiltrating immune cells in the subacute phase after stroke. In this review, we summarize the current state of knowledge on the ATP-adenosine axis in ischemic stroke, discuss contradictory results, and point out potential pitfalls towards translating therapeutic approaches from rodent stroke models to human patients.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"347-365"},"PeriodicalIF":9.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062275","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":"The immunopathology of B lymphocytes during stroke-induced injury and repair.","authors":"Mary K Malone,&nbsp;Thomas A Ujas,&nbsp;Daimen R S Britsch,&nbsp;Katherine M Cotter,&nbsp;Katie Poinsatte,&nbsp;Ann M Stowe","doi":"10.1007/s00281-022-00971-3","DOIUrl":"https://doi.org/10.1007/s00281-022-00971-3","url":null,"abstract":"<p><p>B cells, also known as B lymphocytes or lymphoid lineage cells, are a historically understudied cell population with regard to brain-related injuries and diseases. However, an increasing number of publications have begun to elucidate the different phenotypes and roles B cells can undertake during central nervous system (CNS) pathology, including following ischemic and hemorrhagic stroke. B cell phenotype is intrinsically linked to function following stroke, as they may be beneficial or detrimental depending on the subset, timing, and microenvironment. Factors such as age, sex, and presence of co-morbidity also influence the behavior of post-stroke B cells. The following review will briefly describe B cells from origination to senescence, explore B cell function by integrating decades of stroke research, differentiate between the known B cell subtypes and their respective activity, discuss some of the physiological influences on B cells as well as the influence of B cells on certain physiological functions, and highlight the differences between B cells in healthy and disease states with particular emphasis in the context of ischemic stroke.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"315-327"},"PeriodicalIF":9.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771807","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":"Regulatory T lymphocytes as a therapy for ischemic stroke.","authors":"Miao Wang, Angus W Thomson, Fang Yu, Rimi Hazra, Aditi Junagade, Xiaoming Hu","doi":"10.1007/s00281-022-00975-z","DOIUrl":"10.1007/s00281-022-00975-z","url":null,"abstract":"<p><p>Unrestrained excessive inflammatory responses exacerbate ischemic brain injury and impede post-stroke brain recovery. CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells play important immunosuppressive roles to curtail inflammatory responses and regain immune homeostasis after stroke. Accumulating evidence confirms that Treg cells are neuroprotective at the acute stage after stroke and promote brain repair at the chronic phases. The beneficial effects of Treg cells are mediated by diverse mechanisms involving cell-cell interactions and soluble factor release. Multiple types of cells, including both immune cells and non-immune CNS cells, have been identified to be cellular targets of Treg cells. In this review, we summarize recent findings regarding the function of Treg cells in ischemic stroke and the underlying cellular and molecular mechanisms. The protective and reparative properties of Treg cells endorse them as good candidates for immune therapy. Strategies that boost the numbers and functions of Treg cells have been actively developing in the fields of transplantation and autoimmune diseases. We discuss the approaches for Treg cell expansion that have been tested in stroke models. The application of these approaches to stroke patients may bring new hope for stroke treatments.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 3","pages":"329-346"},"PeriodicalIF":7.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702122","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":"CAR T-cell behavior and function revealed by real-time imaging.","authors":"David Espie,&nbsp;Emmanuel Donnadieu","doi":"10.1007/s00281-023-00983-7","DOIUrl":"https://doi.org/10.1007/s00281-023-00983-7","url":null,"abstract":"<p><p>Adoptive transfer of T-cells expressing chimeric antigen receptors (CAR) has shown remarkable clinical efficacy against advanced B-cell malignancies. Nonetheless, the field of CAR T-cells is currently facing several major challenges. In particular, the CAR T-cell strategy has not yet produced favorable clinical responses when targeting solid tumors. In this context, it is of paramount importance to understand the determinants that limit the efficacy of T-cell-based immunotherapy. Characterization of CAR T-cells is usually based on flow cytometry and whole-transcriptome profiling. These approaches have been very valuable to determine intrinsic elements that condition T-cell ability to proliferate and expand. However, they do not take into account spatial and kinetic aspects of T-cell responses. In particular, in order to control tumor growth, CAR T-cells need to enter into the tumor, migrate within a complex tumor environment, and form productive conjugates with their targets. Advanced imaging techniques combined with innovative preclinical models represent promising tools to uncover the dynamics of CAR T-cells. In this review, we will discuss recent results on the biology of engineered T-cells that have been obtained with real-time imaging microscopy. Important notions have emerged from these imaging-based studies, such as the multi-killing potential of CAR T-cells. Finally, we will highlight how imaging techniques combined with other tools can solve remaining unresolved questions in the field of engineered T-cells.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 2","pages":"229-239"},"PeriodicalIF":9.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677041","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":"Tumor microenvironment antigens.","authors":"Mads Hald Andersen","doi":"10.1007/s00281-022-00966-0","DOIUrl":"https://doi.org/10.1007/s00281-022-00966-0","url":null,"abstract":"<p><p>The identification and characterization of tumor antigens are central objectives in developing anti-cancer immunotherapy. Traditionally, tumor-associated antigens (TAAs) are considered relatively restricted to tumor cells (i.e., overexpressed proteins in tumor cells), whereas tumor-specific antigens (TSAs) are considered unique to tumor cells. Recent studies have focused on identifying patient-specific neoantigens, which might be highly immunogenic because they are not expressed in normal tissues. The opposite strategy has emerged with the discovery of anti-regulatory T cells (anti-Tregs) that recognize and attack many cell types in the tumor microenvironment, such as regulatory immune cells, in addition to tumor cells. The term proposed in this review is \"tumor microenvironment antigens\" (TMAs) to describe the antigens that draw this attack. As therapeutic targets, TMAs offer several advantages that differentiate them from more traditional tumor antigens. Targeting TMAs leads not only to a direct attack on tumor cells but also to modulation of the tumor microenvironment, rendering it immunocompetent and tumor-hostile. Of note, in contrast to TAAs and TSAs, TMAs also are expressed in non-transformed cells with consistent human leukocyte antigen (HLA) expression. Inflammation often induces HLA expression in malignant cells, so that targeting TMAs could additionally affect tumors with no or very low levels of surface HLA expression. This review defines the characteristics, differences, and advantages of TMAs compared with traditional tumor antigens and discusses the use of these antigens in immune modulatory vaccines as an attractive approach to immunotherapy. Different TMAs are expressed by different cells and could be combined in anti-cancer immunotherapies to attack tumor cells directly and modulate local immune cells to create a tumor-hostile microenvironment and inhibit tumor angiogenesis. Immune modulatory vaccines offer an approach for combinatorial therapy with additional immunotherapy including checkpoint blockade, cellular therapy, or traditional cancer vaccines. These combinations would increase the number of patients who can benefit from such therapeutic measures, which all have optimal efficiency in inflamed tumors.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 2","pages":"253-264"},"PeriodicalIF":9.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9830714","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":"Beyond direct killing-novel cellular immunotherapeutic strategies to reshape the tumor microenvironment.","authors":"Duc Huynh,&nbsp;Pia Winter,&nbsp;Florian Märkl,&nbsp;Stefan Endres,&nbsp;Sebastian Kobold","doi":"10.1007/s00281-022-00962-4","DOIUrl":"10.1007/s00281-022-00962-4","url":null,"abstract":"<p><p>The clinical use of cellular immunotherapies is gaining momentum and the number of approved indications is steadily increasing. One class of cellular therapies-chimeric antigen receptor (CAR)-modified T cells-has achieved impressive results in distinct blood cancer indications. These existing cellular therapies treating blood cancers face significant relapse rates, and their application beyond hematology has been underwhelming, especially in solid oncology. Major reasons for resistance source largely in the tumor microenvironment (TME). The TME in fact functionally suppresses, restricts, and excludes adoptive immune cells, which limits the efficacy of cellular immunotherapies from the onset. Many promising efforts are ongoing to adapt cellular immunotherapies to address these obstacles, with the aim of reshaping the tumor microenvironment to ameliorate function and to achieve superior efficacy against both hematological and solid malignancies.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":"45 2","pages":"215-227"},"PeriodicalIF":9.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677007","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}