Pub Date : 2023-07-18DOI: 10.1038/s41577-023-00911-8
K. Maude Ashby, Kristin A. Hogquist
The thymus is an evolutionarily conserved organ that supports the development of T cells. Not only does the thymic environment support the rearrangement and expression of diverse T cell receptors but also provides a unique niche for the selection of appropriate T cell clones. Thymic selection ensures that the repertoire of available T cells is both useful (being MHC-restricted) and safe (being self-tolerant). The unique antigen-presentation features of the thymus ensure that the display of self-antigens is optimal to induce tolerance to all types of self-tissue. MHC class-specific functions of CD4+ T helper cells, CD8+ killer T cells and CD4+ regulatory T cells are also established in the thymus. Finally, the thymus provides signals for the development of several minor T cell subsets that promote immune and tissue homeostasis. This Review provides an introductory-level overview of our current understanding of the sophisticated thymic selection mechanisms that ensure T cells are useful and safe. This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.
胸腺是支持 T 细胞发育的进化保守器官。胸腺环境不仅支持多种 T 细胞受体的重新排列和表达，还为选择合适的 T 细胞克隆提供了独特的环境。胸腺选择可确保可用的 T 细胞群既有用（受 MHC 限制）又安全（具有自我耐受性）。胸腺独特的抗原呈递特征确保了自身抗原的最佳显示，从而诱导对所有类型自身组织的耐受。CD4+ T辅助细胞、CD8+杀伤性T细胞和CD4+调节性T细胞的MHC类特异功能也在胸腺中建立。最后，胸腺为促进免疫和组织稳态的几个次要 T 细胞亚群的发育提供信号。本综述从入门级的角度概述了我们目前对确保 T 细胞有用和安全的复杂胸腺选择机制的理解。
{"title":"A guide to thymic selection of T cells","authors":"K. Maude Ashby, Kristin A. Hogquist","doi":"10.1038/s41577-023-00911-8","DOIUrl":"10.1038/s41577-023-00911-8","url":null,"abstract":"The thymus is an evolutionarily conserved organ that supports the development of T cells. Not only does the thymic environment support the rearrangement and expression of diverse T cell receptors but also provides a unique niche for the selection of appropriate T cell clones. Thymic selection ensures that the repertoire of available T cells is both useful (being MHC-restricted) and safe (being self-tolerant). The unique antigen-presentation features of the thymus ensure that the display of self-antigens is optimal to induce tolerance to all types of self-tissue. MHC class-specific functions of CD4+ T helper cells, CD8+ killer T cells and CD4+ regulatory T cells are also established in the thymus. Finally, the thymus provides signals for the development of several minor T cell subsets that promote immune and tissue homeostasis. This Review provides an introductory-level overview of our current understanding of the sophisticated thymic selection mechanisms that ensure T cells are useful and safe. This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 2","pages":"103-117"},"PeriodicalIF":100.3,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.1038/s41577-023-00919-0
Yvonne Bordon
{"title":"Neutralizing autoantibodies against type 1 interferons identified in West Nile virus encephalitis","authors":"Yvonne Bordon","doi":"10.1038/s41577-023-00919-0","DOIUrl":"10.1038/s41577-023-00919-0","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"476-476"},"PeriodicalIF":100.3,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.1038/s41577-023-00917-2
Yvonne Bordon
{"title":"Thousands of cGAS-like receptors described in animals","authors":"Yvonne Bordon","doi":"10.1038/s41577-023-00917-2","DOIUrl":"10.1038/s41577-023-00917-2","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"476-476"},"PeriodicalIF":100.3,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-14DOI: 10.1038/s41577-023-00907-4
Sarah A. Kent, Veronique E. Miron
Microglia are resident macrophages of the central nervous system that have key functions in its development, homeostasis and response to damage and infection. Although microglia have been increasingly implicated in contributing to the pathology that underpins neurological dysfunction and disease, they also have crucial roles in neurological homeostasis and regeneration. This includes regulation of the maintenance and regeneration of myelin, the membrane that surrounds neuronal axons, which is required for axonal health and function. Myelin is damaged with normal ageing and in several neurodegenerative diseases, such as multiple sclerosis and Alzheimer disease. Given the lack of approved therapies targeting myelin maintenance or regeneration, it is imperative to understand the mechanisms by which microglia support and restore myelin health to identify potential therapeutic approaches. However, the mechanisms by which microglia regulate myelin loss or integrity are still being uncovered. In this Review, we discuss recent work that reveals the changes in white matter with ageing and neurodegenerative disease, how this relates to microglia dynamics during myelin damage and regeneration, and factors that influence the regenerative functions of microglia. Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions.
{"title":"Microglia regulation of central nervous system myelin health and regeneration","authors":"Sarah A. Kent, Veronique E. Miron","doi":"10.1038/s41577-023-00907-4","DOIUrl":"10.1038/s41577-023-00907-4","url":null,"abstract":"Microglia are resident macrophages of the central nervous system that have key functions in its development, homeostasis and response to damage and infection. Although microglia have been increasingly implicated in contributing to the pathology that underpins neurological dysfunction and disease, they also have crucial roles in neurological homeostasis and regeneration. This includes regulation of the maintenance and regeneration of myelin, the membrane that surrounds neuronal axons, which is required for axonal health and function. Myelin is damaged with normal ageing and in several neurodegenerative diseases, such as multiple sclerosis and Alzheimer disease. Given the lack of approved therapies targeting myelin maintenance or regeneration, it is imperative to understand the mechanisms by which microglia support and restore myelin health to identify potential therapeutic approaches. However, the mechanisms by which microglia regulate myelin loss or integrity are still being uncovered. In this Review, we discuss recent work that reveals the changes in white matter with ageing and neurodegenerative disease, how this relates to microglia dynamics during myelin damage and regeneration, and factors that influence the regenerative functions of microglia. Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 1","pages":"49-63"},"PeriodicalIF":100.3,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-11DOI: 10.1038/s41577-023-00904-7
Daniel M. Altmann, Emily M. Whettlock, Siyi Liu, Deepa J. Arachchillage, Rosemary J. Boyton
Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways. SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore current thinking about the pathophysiology of long COVID and discuss potential immunological mechanisms.
{"title":"The immunology of long COVID","authors":"Daniel M. Altmann, Emily M. Whettlock, Siyi Liu, Deepa J. Arachchillage, Rosemary J. Boyton","doi":"10.1038/s41577-023-00904-7","DOIUrl":"10.1038/s41577-023-00904-7","url":null,"abstract":"Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein–Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways. SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore current thinking about the pathophysiology of long COVID and discuss potential immunological mechanisms.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 10","pages":"618-634"},"PeriodicalIF":100.3,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41577-023-00904-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-10DOI: 10.1038/s41577-023-00916-3
Kirsty Minton
In contrast to its role in promoting immune responses to viral and bacterial infections, STING inhibits SYK-dependent cytokine production in response to fungal infection.
{"title":"Negative regulation of fungal immunity by STING","authors":"Kirsty Minton","doi":"10.1038/s41577-023-00916-3","DOIUrl":"10.1038/s41577-023-00916-3","url":null,"abstract":"In contrast to its role in promoting immune responses to viral and bacterial infections, STING inhibits SYK-dependent cytokine production in response to fungal infection.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"475-475"},"PeriodicalIF":100.3,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-04DOI: 10.1038/s41577-023-00914-5
Yvonne Bordon
Bacteria that cause cholera can form unique biofilms on immune cells to promote immune cell death.
导致霍乱的细菌可以在免疫细胞上形成独特的生物膜，促进免疫细胞死亡。
{"title":"Bacteria form unique biofilms to kill immune cells","authors":"Yvonne Bordon","doi":"10.1038/s41577-023-00914-5","DOIUrl":"10.1038/s41577-023-00914-5","url":null,"abstract":"Bacteria that cause cholera can form unique biofilms on immune cells to promote immune cell death.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"474-474"},"PeriodicalIF":100.3,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer–immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies — including scaffolds, organoids, microfluidics and 3D bioprinting — and thirdly, on the applications of these 3D models for comprehending the cancer–immunity cycle as well as for assessing and improving immunotherapies for solid tumours. This Review describes recent advances in the field of 3D in vitro modelling technologies that enable a better understanding of immune cell and tumour cell interactions in the tumour microenvironment. The authors explain how such systems can be used to assess the efficacy of novel immunotherapies, including personalized immunotherapies, for patients with cancer.
{"title":"Harnessing 3D in vitro systems to model immune responses to solid tumours: a step towards improving and creating personalized immunotherapies","authors":"Zhenzhen Zhou, Yuan Pang, Jingyuan Ji, Jianyu He, Tiankun Liu, Liliang Ouyang, Wen Zhang, Xue-Li Zhang, Zhi-Gang Zhang, Kaitai Zhang, Wei Sun","doi":"10.1038/s41577-023-00896-4","DOIUrl":"10.1038/s41577-023-00896-4","url":null,"abstract":"In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer–immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies — including scaffolds, organoids, microfluidics and 3D bioprinting — and thirdly, on the applications of these 3D models for comprehending the cancer–immunity cycle as well as for assessing and improving immunotherapies for solid tumours. This Review describes recent advances in the field of 3D in vitro modelling technologies that enable a better understanding of immune cell and tumour cell interactions in the tumour microenvironment. The authors explain how such systems can be used to assess the efficacy of novel immunotherapies, including personalized immunotherapies, for patients with cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 1","pages":"18-32"},"PeriodicalIF":100.3,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9807474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-04DOI: 10.1038/s41577-023-00915-4
Lucy Bird
A new population of macrophages is identified in mice that expands during lactation and may be important in immune surveillance.
在小鼠体内发现了一种新的巨噬细胞群，这种巨噬细胞群在哺乳期不断扩大，可能在免疫监视中起着重要作用。
{"title":"Lactation-associated macrophages","authors":"Lucy Bird","doi":"10.1038/s41577-023-00915-4","DOIUrl":"10.1038/s41577-023-00915-4","url":null,"abstract":"A new population of macrophages is identified in mice that expands during lactation and may be important in immune surveillance.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"23 8","pages":"476-476"},"PeriodicalIF":100.3,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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