{"title":"The gut mucus network: A dynamic liaison between microbes and the immune system","authors":"Rain Inaba, Sara Vujakovic, Kirk Bergstrom","doi":"10.1016/j.smim.2023.101807","DOIUrl":"10.1016/j.smim.2023.101807","url":null,"abstract":"<div><p>A complex mucus network made up of large polymers of the mucin-family glycoprotein MUC2 exists between the large intestinal microbial mass and epithelial and immune cells. This has long been understood as an innate immune defense barrier against the microbiota and other luminal threats that reinforces the barrier function of the epithelium and limits microbiota contact with the tissues. However, past and recent studies have provided new evidence of how critical the mucus network is to act as a ‘liaison’ between host and microbe to mediate anti-inflammatory, mutualistic interactions with the microbiota and protection from pathogens. This review summarizes historical and recent insights into the formation of the gut mucus network, how the microbes and immune system influence mucus, and in turn, how the mucus influences immune responses to the microbiota.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101807"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169067","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":"Age-dependent changes in T follicular helper cells shape the humoral immune response to vaccination","authors":"Michelle A. Linterman","doi":"10.1016/j.smim.2023.101801","DOIUrl":"10.1016/j.smim.2023.101801","url":null,"abstract":"<div><p>Vaccination is an excellent strategy to limit the morbidity and mortality associated with infectious disease. Vaccination creates protective, long-lived antibody-mediated immunity by inducing the germinal centre response, an intricate immune reaction that produces memory B cells and long-lived antibody-secreting plasma cells that provide protection against (re)infection. The magnitude and quality of the germinal centre response declines with age, contributing to poor vaccine-induced immunity in older individuals. T follicular helper cells are essential for the formation and function of the germinal centre response. This review will discuss how age-dependent changes in T follicular helper cells influence the germinal centre response, and the evidence that age-dependent changes need not be a barrier to successful vaccination in the later years of life.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101801"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10221868","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":"Numbers and odds: TCR repertoire size and its age changes impacting on T cell functions","authors":"Nan-ping Weng","doi":"10.1016/j.smim.2023.101810","DOIUrl":"10.1016/j.smim.2023.101810","url":null,"abstract":"<div><p>A vast array of αβ T cell receptors (TCRs) is generated during T cell development in the thymus through V(D)J recombination, which involves the rearrangement of multiple V, D, and J genes and the pairing of α and β chains. These diverse TCRs provide protection to the human body against a multitude of foreign pathogens and internal cancer cells. The entirety of TCRs present in an individual's T cells is referred to as the TCR repertoire. Despite an estimated 4 × 10<sup>11</sup> T cells in the adult human body, the lower bound estimate for the TCR repertoire is 3.8 × 10<sup>8</sup>. While the number of circulating T cells may slightly decrease with age, the changes in the diversity of the TCR repertoire is more apparent. Here, I review recent advancements in TCR repertoire studies, the methods used to measure it, how richness and diversity change as humans age, and some of the known consequences associated with these changes.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"69 ","pages":"Article 101810"},"PeriodicalIF":7.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223114","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":"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}
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}
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}
{"title":"T cell control of SARS-CoV-2: When, which, and where?","authors":"Mariana O. Diniz, Mala K. Maini, Leo Swadling","doi":"10.1016/j.smim.2023.101828","DOIUrl":"10.1016/j.smim.2023.101828","url":null,"abstract":"<div><p>Efficient immune protection against viruses such as SARS-CoV-2 requires the coordinated activity of innate immunity, B and T cells. Accumulating data point to a critical role for T cells not only in the clearance of established infection, but also for aborting viral replication independently of humoral immunity. Here we review the evidence supporting the contribution of antiviral T cells and consider which of their qualitative features favour efficient control of infection. We highlight how studies of SARS-CoV-2 and other <em>coronaviridae</em> in animals and humans have provided important lessons on the optimal timing (When), functionality and specificity (Which), and location (Where) of antiviral T cells. We discuss the clinical implications, particularly for the development of next-generation vaccines, and emphasise areas requiring further study.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101828"},"PeriodicalIF":7.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119264","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":"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}
Lies van Baarle, Michelle Stakenborg, Gianluca Matteoli
{"title":"Enteric neuro-immune interactions in intestinal health and disease","authors":"Lies van Baarle, Michelle Stakenborg, Gianluca Matteoli","doi":"10.1016/j.smim.2023.101819","DOIUrl":"10.1016/j.smim.2023.101819","url":null,"abstract":"<div><p>The enteric nervous system is an autonomous neuronal circuit that regulates many processes far beyond the peristalsis in the gastro-intestinal tract. This circuit, consisting of enteric neurons and enteric glial cells, can engage in many intercellular interactions shaping the homeostatic microenvironment in the gut. Perhaps the most well documented interactions taking place, are the intestinal neuro-immune interactions which are essential for the fine-tuning of oral tolerance. In the context of intestinal disease, compelling evidence demonstrates both protective and detrimental roles for this bidirectional neuro-immune signaling. This review discusses the different immune cell types that are recognized to engage in neuronal crosstalk during intestinal health and disease. Highlighting the molecular pathways involved in the neuro-immune interactions might inspire novel strategies to target intestinal disease.</p></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"70 ","pages":"Article 101819"},"PeriodicalIF":7.8,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10079109","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}
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}