Seminars in Immunology最新文献_第7页

Thymus aging and immune reconstitution, progresses and challenges 胸腺老化与免疫重建、进展与挑战

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-31 DOI: 10.1016/j.smim.2023.101837

Yue Ru Li , Juan Carlos Zúñiga-Pflücker

{"title":"Thymus aging and immune reconstitution, progresses and challenges","authors":"Yue Ru Li , Juan Carlos Zúñiga-Pflücker","doi":"10.1016/j.smim.2023.101837","DOIUrl":"10.1016/j.smim.2023.101837","url":null,"abstract":"<div><p>Thymus is a primary lymphoid organ essential for the development of T lymphocytes. Age-related thymic involution is a prominent feature of immune senescence. The thymus undergoes rapid growth during fetal and neonatal development, peaks in size before puberty and then begins to undergo a decrease in cellularity with age. Dramatic changes occur with age-associated thymic involution. The most prominent features of thymic involution include: (i) epithelial structure disruption, (ii) adipogenesis, and (iii) thymocyte development arrest. There is a sex disparity in thymus aging. It is a multifactorial process controlled and regulated by a series of molecules, including the transcription factor FOXN1, fibroblast and keratinocyte growth factors (FGF and KGF, respectively), sex steroids, Notch signaling, WNT signaling, and microRNAs. Nevertheless, there is still no satisfactory evolutionary or physiological explanation for age-associated thymic involution, and understanding the precise mechanism(s) for thymus aging remains challenging. Sustained thymic regeneration has yet to be achieved by sex steroid ablation. Recent preclinical studies indicate that long-term thymic reconstitution can be achieved via adoptive transfer of <em>in vitro</em>-generated progenitor T (proT) cells, and improvements in the methods for the generation of human proT cells make this an attractive approach. Future clinical applications may rely on new applications integrating proT cells, cytokine support and sex-steroid inhibition treatments.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101837"},"PeriodicalIF":7.8,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139969","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}

引用次数: 0

The paradox of aging: Aging-related shifts in T cell function and metabolism 衰老的悖论:与衰老相关的T细胞功能和代谢的变化

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-31 DOI: 10.1016/j.smim.2023.101834

Kylie M. Quinn , Daniela M. Vicencio , Nicole L. La Gruta

{"title":"The paradox of aging: Aging-related shifts in T cell function and metabolism","authors":"Kylie M. Quinn , Daniela M. Vicencio , Nicole L. La Gruta","doi":"10.1016/j.smim.2023.101834","DOIUrl":"10.1016/j.smim.2023.101834","url":null,"abstract":"<div><p>T cell survival, differentiation after stimulation, and function are intrinsically linked to distinct cellular metabolic states. The ability of T cells to readily transition between metabolic states enables flexibility to meet the changing energy demands defined by distinct effector states or T cell lineages. Immune aging is characterized, in part, by the loss of naïve T cells, accumulation of senescent T cells, severe dysfunction in memory phenotype T cells in particular, and elevated levels of inflammatory cytokines, or ‘inflammaging’. Here, we review our current understanding of the phenotypic and functional changes that occur with aging in T cells, and how they relate to metabolic changes in the steady state and after T cell activation. We discuss the apparent contradictions in the aging T cell phenotype - where enhanced differentiation states and metabolic profiles in the steady state can correspond to a diminished capacity to adapt metabolically and functionally after T cell activation. Finally, we discuss key recent studies that indicate the enormous potential for aged T cell metabolism to induce systemic inflammaging and organism-wide multimorbidity, resulting in premature death.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101834"},"PeriodicalIF":7.8,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139975","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}

引用次数: 0

Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging 次级淋巴器官组织紊乱和趋化因子分泌失调是免疫衰老的关键因素

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-29 DOI: 10.1016/j.smim.2023.101835

Sandip Ashok Sonar , Makiko Watanabe , Janko Ž. Nikolich

{"title":"Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging","authors":"Sandip Ashok Sonar , Makiko Watanabe , Janko Ž. Nikolich","doi":"10.1016/j.smim.2023.101835","DOIUrl":"10.1016/j.smim.2023.101835","url":null,"abstract":"<div><p>Aging is characterized by progressive loss of organ and tissue function, and the immune system is no exception to that inevitable principle. Of all the age-related changes in the body, reduction of the size of, and naïve T (Tn) cell output from, the thymus occurs earliest, being prominent already before or by the time of puberty. Therefore, to preserve immunity against new infections, over much of their lives, vertebrates dominantly rely on peripheral maintenance of the Tn cell pool in the secondary lymphoid organs (SLO). However, SLO structure and function subsequently also deteriorate with aging. Several recent studies have made a convincing case that this deterioration is of major importance to the erosion of protective immunity in the last third of life. Specifically, the SLO were found to accumulate multiple degenerative changes with aging. Importantly, the results from adoptive transfer and parabiosis studies teach us that the old microenvironment is the limiting factor for protective immunity in old mice. In this review, we discuss the extent, mechanisms, and potential role of stromal cell aging in the age-related alteration of T cell homeostatic maintenance and immune function decline. We use that discussion to frame the potential strategies to correct the SLO stromal aging defects - in the context of other immune rejuvenation approaches, - to improve functional immune responses and protective immunity in older adults.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101835"},"PeriodicalIF":7.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119259","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}

引用次数: 0

T cell control of SARS-CoV-2: When, which, and where? T细胞控制SARS-CoV-2的时间、方式和地点?

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-29 DOI: 10.1016/j.smim.2023.101828

Mariana O. Diniz, Mala K. Maini, Leo Swadling

引用次数: 0

Gasdermins and cancers Gasdermins和癌症

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-28 DOI: 10.1016/j.smim.2023.101833

Junwei Hou , Tiansheng Li , Jung-Mao Hsu , Xin Zhang , Mien-Chie Hung

{"title":"Gasdermins and cancers","authors":"Junwei Hou , Tiansheng Li , Jung-Mao Hsu , Xin Zhang , Mien-Chie Hung","doi":"10.1016/j.smim.2023.101833","DOIUrl":"10.1016/j.smim.2023.101833","url":null,"abstract":"<div><p>The identification of gasdermin as the executor of pyroptosis has opened new avenues for the study of this process. Although pyroptosis research has mainly focused on immune cells since it was discovered three decades ago, accumulating evidence suggests that pyroptosis plays crucial roles in many biological processes. One example is the discovery of gasdermin-mediated cancer cell pyroptosis (CCP) which has become an important and frontier field in oncology. Recent studies have shown that CCP induction can heat tumor microenvironment (TME) and thereby elicit the robust anti-tumor immunity to suppress tumor growth. As a newly discovered form of tumor cell death, CCP offers promising opportunities for improving tumor treatment and developing new drugs. Nevertheless, the research on CCP is still in its infancy, and the molecular mechanisms underlying the expression, regulation and activation of gasdermins are not yet fully understood. In this review, we summarize the recent progress of gasdermin research in cancer area, and propose that the anti-tumor effect of immune cell pyroptosis (ICP) and CCP depends on their duration, intensity, and the type of cells undergoing pyroptosis within TME.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101833"},"PeriodicalIF":7.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476390","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}

引用次数: 0

Enteric neuro-immune interactions in intestinal health and disease 肠道健康和疾病中的肠道神经免疫相互作用

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-25 DOI: 10.1016/j.smim.2023.101819

Lies van Baarle, Michelle Stakenborg, Gianluca Matteoli

引用次数: 0

Accumulation of immune-suppressive CD4 + T cells in aging – tempering inflammaging at the expense of immunity 免疫抑制性CD4+T细胞在衰老中的积累——以牺牲免疫力为代价的炎症调节。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-24 DOI: 10.1016/j.smim.2023.101836

Alyssa L. Thomas , Alzbeta Godarova , Joseph A. Wayman , Emily R. Miraldi , David A. Hildeman , Claire A. Chougnet

{"title":"Accumulation of immune-suppressive CD4 + T cells in aging – tempering inflammaging at the expense of immunity","authors":"Alyssa L. Thomas , Alzbeta Godarova , Joseph A. Wayman , Emily R. Miraldi , David A. Hildeman , Claire A. Chougnet","doi":"10.1016/j.smim.2023.101836","DOIUrl":"10.1016/j.smim.2023.101836","url":null,"abstract":"<div><p>The 'immune risk profile' has been shown to predict mortality in the elderly, highlighting the need to better understand age-related immune dysfunction. While aging leads to many defects affecting all arms of the immune system, this review is focused on the accrual of immuno-suppressive CD4 + T cell populations, including FoxP3 + regulatory T cells, and subsets of IL-10-producing T follicular helper cells. New data suggest that such accumulations constitute feedback mechanisms to temper the ongoing progressive low-grade inflammation that develops with age, the so-called “inflammaging”, and by doing so, how they have the potential to promote healthier aging. However, they also impair effector immune responses, notably to infections, or vaccines. These studies also reinforce the idea that the aged immune system should not be considered as a poorly functional version of the young one, but more as a dynamic system in which CD4 + T cells, and other immune/non-immune subsets, differentiate, interact with their milieu and function differently than in young hosts. A better understanding of these unique interactions is thus needed to improve effector immune responses in the elderly, while keeping inflammaging under control.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101836"},"PeriodicalIF":7.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073434","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}

引用次数: 0

The role of caspase-8 in inflammatory signalling and pyroptotic cell death caspase-8在炎症信号传导和焦亡细胞死亡中的作用

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-23 DOI: 10.1016/j.smim.2023.101832

Jiyi Pang , James E. Vince

{"title":"The role of caspase-8 in inflammatory signalling and pyroptotic cell death","authors":"Jiyi Pang , James E. Vince","doi":"10.1016/j.smim.2023.101832","DOIUrl":"10.1016/j.smim.2023.101832","url":null,"abstract":"<div><p>The programmed cell death machinery exhibits surprising flexibility, capable of crosstalk and non-apoptotic roles. Much of this complexity arises from the diverse functions of caspase-8, a cysteine-aspartic acid protease typically associated with activating caspase-3 and − 7 to induce apoptosis. However, recent research has revealed that caspase-8 also plays a role in regulating the lytic gasdermin cell death machinery, contributing to pyroptosis and immune responses in contexts such as infection, autoinflammation, and T-cell signalling. In mice, loss of caspase-8 results in embryonic lethality from unrestrained necroptotic killing, while in humans caspase-8 deficiency can lead to an autoimmune lymphoproliferative syndrome, immunodeficiency, inflammatory bowel disease or, when it can’t cleave its substrate RIPK1, early onset periodic fevers. This review focuses on non-canonical caspase-8 signalling that drives immune responses, including its regulation of inflammatory gene transcription, activation within inflammasome complexes, and roles in pyroptotic cell death. Ultimately, a deeper understanding of caspase-8 function will aid in determining whether, and when, targeting caspase-8 pathways could be therapeutically beneficial in human diseases.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101832"},"PeriodicalIF":7.8,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10074141","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}

引用次数: 0

T cell control of inflammaging T细胞控制炎症

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-21 DOI: 10.1016/j.smim.2023.101818

Irina Shchukina, Pavla Bohacova, Maxim N. Artyomov

引用次数: 0

Aging of lymphoid stromal architecture impacts immune responses 淋巴基质结构老化影响免疫反应

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2023-08-10 DOI: 10.1016/j.smim.2023.101817

Jessica N. Lancaster

{"title":"Aging of lymphoid stromal architecture impacts immune responses","authors":"Jessica N. Lancaster","doi":"10.1016/j.smim.2023.101817","DOIUrl":"10.1016/j.smim.2023.101817","url":null,"abstract":"<div><p>The secondary lymphoid organs (SLOs) undergo structural changes with age, which correlates with diminishing immune responses against infectious disease. A growing body of research suggests that the aged tissue microenvironment can contribute to decreased immune function, independent of intrinsic changes to hematopoietic cells with age. Stromal cells impart structural integrity, facilitate fluid transport, and provide chemokine and cytokine signals that are essential for immune homeostasis. Mechanisms that drive SLO development have been described, but their roles in SLO maintenance with advanced age are unknown. Disorganization of the fibroblasts of the T cell and B cell zones may reduce the maintenance of naïve lymphocytes and delay immune activation. Reduced lymphatic transport efficiency with age can also delay the onset of the adaptive immune response. This review focuses on recent studies that describe age-associated changes to the stroma of the lymph nodes and spleen. We also review recent investigations into stromal cell biology, which include high-dimensional analysis of the stromal cell transcriptome and viscoelastic testing of lymph node mechanical properties, as they constitute an important framework for understanding aging of the lymphoid tissues.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101817"},"PeriodicalIF":7.8,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972826","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}

引用次数: 0