Immunological Reviews最新文献

{"title":"The multifaceted life of macrophages in white adipose tissue: Immune shift couples with metabolic switch","authors":"Qun Wang,&nbsp;Sean M. Hartig,&nbsp;Christie M. Ballantyne,&nbsp;Huaizhu Wu","doi":"10.1111/imr.13338","DOIUrl":"10.1111/imr.13338","url":null,"abstract":"<div>\u0000 \u0000 <p>White adipose tissue (WAT) is a vital endocrine organ that regulates energy balance and metabolic homeostasis. In addition to fat cells, WAT harbors macrophages with distinct phenotypes that play crucial roles in immunity and metabolism. Nutrient demands cause macrophages to accumulate in WAT niches, where they remodel the microenvironment and produce beneficial or detrimental effects on systemic metabolism. Given the abundance of macrophages in WAT, this review summarizes the heterogeneity of WAT macrophages in physiological and pathological conditions, including their alterations in quantity, phenotypes, characteristics, and functions during WAT growth and development, as well as healthy or unhealthy expansion. We will discuss the interactions of macrophages with other cell partners in WAT including adipose stem cells, adipocytes, and T cells in the context of various microenvironment niches in lean or obese condition. Finally, we highlight how adipose tissue macrophages merge immunity and metabolic changes to govern energy balance for the organism.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"324 1","pages":"11-24"},"PeriodicalIF":7.5,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840761","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":"Deciphering visceral adipose tissue regulatory T cells: Key contributors to metabolic health","authors":"Cody Elkins,&nbsp;Chaoran Li","doi":"10.1111/imr.13336","DOIUrl":"10.1111/imr.13336","url":null,"abstract":"<div>\u0000 \u0000 <p>Regulatory T cells (Tregs) within the visceral adipose tissue (VAT) play a crucial role in controlling tissue inflammation and maintaining metabolic health. VAT Tregs display a unique transcriptional profile and T cell receptor (TCR) repertoire, and closely interact with adipocytes, stromal cells, and other immune components within the local VAT microenvironment. However, in the context of obesity, there is a notable decline in VAT Tregs, resulting in heightened VAT inflammation and insulin resistance. A comprehensive understanding of the biology of VAT Tregs is essential for the development of Treg-based therapies for mitigating obesity-associated metabolic diseases. Recent advancements in lineage tracing tools, genetic mouse models, and various single cell “omics” techniques have significantly progressed our understandings of the origin, differentiation, and regulation of this unique VAT Treg population at steady state and during obesity. The identification of VAT-Treg precursor cells in the secondary lymphoid organs has also provided important insights into the timing, location, and mechanisms through which VAT Tregs acquire their distinctive phenotype that enables them to function within a lipid-rich microenvironment. In this review, we highlight key recent breakthroughs in the VAT-Treg field while discussing pivotal questions that remain unanswered.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"324 1","pages":"52-67"},"PeriodicalIF":7.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652478","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":"Development and organization of omental milky spots","authors":"Yasutaka Okabe","doi":"10.1111/imr.13337","DOIUrl":"10.1111/imr.13337","url":null,"abstract":"<p>The milky spots in omentum are atypical lymphoid tissues that play a pivotal role in regulating immune responses in the peritoneal cavity. The milky spots act as central hubs for collecting antigens and particles from the peritoneal cavity, regulating lymphocyte trafficking, promoting the differentiation and self-renewal of immune cells, and supporting the local germinal centre response. In addition, the milky spots exhibit unique developmental characteristics that combine the features of secondary and tertiary lymphoid tissues. These structures are innately programmed to form during foetal development; however, they can also be formed postnatally in response to peritoneal irritation such as inflammation, infection, obesity, or tumour metastasis. In this review, I discuss emerging perspectives on homeostatic development and organization of the milky spots.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"324 1","pages":"68-77"},"PeriodicalIF":7.5,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655200","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":"Innate immunity—With an adaptive twist","authors":"Steven Z. Josefowicz,&nbsp;Joseph C. Sun","doi":"10.1111/imr.13334","DOIUrl":"10.1111/imr.13334","url":null,"abstract":"&lt;p&gt;Decades of discovery have led immunologists to compartmentalize the mammalian immune system into two components: innate and adaptive immunity. The textbooks and traditional viewpoint describe the innate immune system as rapid and non-specific, whereas the adaptive immune system consisting of T and B cells is delayed but specific and possessing memory. Every immune cell type that is not a T or B cell is broadly lumped under the umbrella of innate immunity. However, recent research has shown us that certain innate immune cells can possess features of adaptive immunity, including immunological memory.&lt;/p&gt;&lt;p&gt;Anecdotal evidence of memory in the innate immune system—a memory independent of T and B cell-mediated antigen-specific memory—has existed for a century or more and included observations in plants and animals, including humans. Only recently, however, have the specific cellular and molecular mechanisms started to emerge, highlighting fundamentals of immunity and previously unknown functional ‘levers’ that tune immune tone. The key cellular players, natural killer (NK) cells and myeloid cells, are found at the forefront of this paradigm-shifting revolution and central to this volume of Immunological Reviews. Two decades ago, NK cells were first shown to possess adaptive immune features from antigen specificity to clonal expansion to long-lived memory to recall responses. Next, myeloid cells were proposed to possess anamnestic responses after initial stimulation in a process termed “trained immunity.” Although our understanding of the mechanisms driving such adaptive characteristics in innate immune cells has expanded in recent years, there is still much to be learned about the important features of innate immune memory. Future studies will illuminate additional external signals inducing durable memory, cellular and metabolic processes required, underlying transcription factor and epigenetic programs and their durability, and finally the impact on health and disease.&lt;/p&gt;&lt;p&gt;The first group of reviews in this volume address how mouse and human NK cells respond to various environmental stimuli that program their clonality, gene expression, metabolism, effector function, survival, trafficking, tissue residency, and memory. Reviews from Delconte and Sun&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and Ashkar and colleagues,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; focus on underlying organ-specific metabolic mechanisms in mouse and human NK cells, respectively, in the contexts of nutrition and health versus host perturbations including fasting, infection, and cancer. Aguilar and Lanier&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; highlight how adaptive features of NK cells including clonal expansion depend upon specific signaling via ITAM-containing receptors. Reviews from Degli-Esposti and colleagues,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Hermans and O'Sullivan,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; and Ruckert and Romagnani&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; focus on the selection of mouse and human NK cell clones to be epigenetically pri","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"5-7"},"PeriodicalIF":8.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611424","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":"Metabolic programming of organ-specific natural killer cell responses","authors":"Rebecca B. Delconte,&nbsp;Joseph C. Sun","doi":"10.1111/imr.13333","DOIUrl":"10.1111/imr.13333","url":null,"abstract":"<div>\u0000 \u0000 <p>Cells of the mammalian innate immune system have evolved to protect the host from various environmental or internal insults and injuries which perturb the homeostatic state of the organism. Among the lymphocytes of the innate immune system are natural killer (NK) cells, which circulate and survey host tissues for signs of stress, including infection or transformation. NK cells rapidly eliminate damaged cells in the blood or within tissues through secretion of cytolytic machinery and production of proinflammatory cytokines. To perform these effector functions while traversing between the blood and tissues, patrolling NK cells require sufficient fuel to meet their energetic demands. Here, we highlight the ability of NK cells to metabolically adapt across tissues, during times of nutrient deprivation and within tumor microenvironments. Whether at steady state, or during viral infection and cancer, NK cells readily shift their nutrient uptake and usage in order to maintain metabolism, survival, and function.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"8-18"},"PeriodicalIF":8.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611309","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 potency of hematopoietic stem cell reprogramming for changing immune tone","authors":"Andrew W. Daman,&nbsp;Jin Gyu Cheong,&nbsp;Laura Berneking,&nbsp;Steven Z. Josefowicz","doi":"10.1111/imr.13335","DOIUrl":"10.1111/imr.13335","url":null,"abstract":"<div>\u0000 \u0000 <p>Innate immune memory endows innate immune cells with antigen independent heightened responsiveness to subsequent challenges. The durability of this response can be mediated by inflammation induced epigenetic and metabolic reprogramming in hematopoietic stem and progenitor cells (HSPCs) that are maintained through differentiation to mature immune progeny. Understanding the mechanisms and extent of trained immunity induction by pathogens and vaccines, such as BCG, in HSPC remains a critical area of exploration with important implications for health and disease. Here we review these concepts and present new analysis to highlight how inflammatory reprogramming of HSPC can potently alter immune tone, including to enhance specific anti-tumor responses. New findings in the field pave the way for novel HSPC targeting therapeutic strategies in cancer and other contexts of immune modulation. Future studies are expected to unravel diverse and extensive effects of infections, vaccines, microbiota, and sterile inflammation on hematopoietic progenitor cells and begin to illuminate the broad spectrum of immunologic tuning that can be established through altering HSPC phenotypes. The purpose of this review is to draw attention to emerging and speculative topics in this field where we posit that focused study of HSPC in the framework of trained immunity holds significant promise.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"197-208"},"PeriodicalIF":8.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625959","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":"Shaping immunity: The influence of natural selection on population immune diversity","authors":"Haley E. Randolph,&nbsp;Katherine A. Aracena,&nbsp;Yen-Lung Lin,&nbsp;Zepeng Mu,&nbsp;Luis B. Barreiro","doi":"10.1111/imr.13329","DOIUrl":"10.1111/imr.13329","url":null,"abstract":"<p>Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present-day susceptibility to immune-related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"227-240"},"PeriodicalIF":8.7,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577775","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":"Interferons and epigenetic mechanisms in training, priming and tolerance of monocytes and hematopoietic progenitors","authors":"Bikash Mishra,&nbsp;Lionel B. Ivashkiv","doi":"10.1111/imr.13330","DOIUrl":"10.1111/imr.13330","url":null,"abstract":"<div>\u0000 \u0000 <p>Training and priming of innate immune cells involve preconditioning by PAMPs, DAMPs, and/or cytokines that elicits stronger induction of inflammatory genes upon secondary challenge. Previous models distinguish training and priming based upon whether immune activation returns to baseline prior to secondary challenge. Tolerance is a protective mechanism whereby potent stimuli induce refractoriness to secondary challenge. Training and priming are important for innate memory responses that protect against infection, efficacy of vaccines, and maintaining innate immune cells in a state of readiness; tolerance prevents toxicity from excessive immune activation. Dysregulation of these processes can contribute to pathogenesis of autoimmune/inflammatory conditions, post-COVID-19 hyperinflammatory states, or sepsis-associated immunoparalysis. Training, priming, and tolerance regulate similar “signature” inflammatory genes such as <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> and utilize overlapping epigenetic mechanisms. We review how interferons (IFNs), best known for activating JAK–STAT signaling and interferon-stimulated genes, also play a key role in regulating training, priming, and tolerance via chromatin-mediated mechanisms. We present new data on how monocyte-to-macrophage differentiation modulates IFN-γ-mediated priming, affects regulation of AP-1 and CEBP activity, and attenuates superinduction of inflammatory genes. We present a “training-priming continuum” model that integrates IFN-mediated priming into current concepts about training and tolerance and proposes a central role for STAT1 and IRF1.</p>\u0000 </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"257-275"},"PeriodicalIF":8.7,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577771","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":"Tissue-resident memory NK cells: Homing in on local effectors and regulators","authors":"Iona S. Schuster,&nbsp;Christopher E. Andoniou,&nbsp;Mariapia A. Degli-Esposti","doi":"10.1111/imr.13332","DOIUrl":"10.1111/imr.13332","url":null,"abstract":"<p>Natural killer (NK) cells are the prototype innate effector lymphocyte population that plays an important role in controlling viral infections and tumors. Studies demonstrating that NK cells form long-lived memory populations, akin to those generated by adaptive immune cells, prompted a revaluation of the potential functions of NK cells. Recent data demonstrating that NK cells are recruited from the circulation into tissues where they form long-lived memory-like populations further emphasize that NK cells have properties that mirror those of adaptive immune cells. NK cells that localize in non-lymphoid tissues are heterogeneous, and there is a growing appreciation that immune responses occurring within tissues are subject to tissue-specific regulation. Here we discuss both the immune effector and immunoregulatory functions of NK cells, with a particular emphasis on the role of NK cells within non-lymphoid tissues and how the tissue microenvironment shapes NK cell-dependent outcomes.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"54-60"},"PeriodicalIF":8.7,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577787","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":"Discovering adaptive features of innate immune memory","authors":"Mina Sadeghi,&nbsp;Maziar Divangahi","doi":"10.1111/imr.13328","DOIUrl":"10.1111/imr.13328","url":null,"abstract":"<p>Conventionally, it was thought that innate immunity operated through a simple system of nonspecific responses to an insult. However, this perspective now seems overly simplistic. It has become evident that intricate cooperation and networking among various cells, receptors, signaling pathways, and protein complexes are essential for regulating and defining the overall activation status of the immune response, where the distinction between innate and adaptive immunity becomes ambiguous. Given the evolutionary timeline of vertebrates and the success of plants and invertebrates which depend solely on innate immunity, immune memory cannot be considered an innovation of only the lymphoid lineage. Indeed, the evolutionary innate immune memory program is a conserved mechanism whereby innate immune cells can induce a heightened response to a secondary stimulus due to metabolic and epigenetic reprogramming. Importantly, the longevity of this memory phenotype can be attributed to the reprogramming of self-renewing hematopoietic stem cells (HSCs) in the bone marrow, which is subsequently transmitted to lineage-committed innate immune cells. HSCs reside within a complex regulated network of immune and stromal cells that govern their two primary functions: self-renewal and differentiation. In this review, we delve into the emerging cellular and molecular mechanisms as well as metabolic pathways of innate memory in HSCs, which harbor substantial therapeutic promise.</p>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"323 1","pages":"186-196"},"PeriodicalIF":8.7,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imr.13328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334057","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}