Pub Date : 2024-05-24DOI: 10.1038/s41577-024-01050-4
Anthony Altieri, Matthew B. Buechler
A preprint by Ben-Chetrit et al. investigates the molecular and cellular mechanisms that regulate macrophage heterogeneity in solid breast cancer tumours.
Ben-Chetrit 等人的预印本研究了调控乳腺癌实体瘤中巨噬细胞异质性的分子和细胞机制。
{"title":"Breast cancer-associated fibroblasts maintain self-renewing immunosuppressive macrophages","authors":"Anthony Altieri, Matthew B. Buechler","doi":"10.1038/s41577-024-01050-4","DOIUrl":"10.1038/s41577-024-01050-4","url":null,"abstract":"A preprint by Ben-Chetrit et al. investigates the molecular and cellular mechanisms that regulate macrophage heterogeneity in solid breast cancer tumours.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093565","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 : 2024-05-24DOI: 10.1038/s41577-024-01052-2
Kirsty Minton
Two papers in Immunity report the effects of acetylcholine secretion by intestinal tuft cells on epithelial cells and helminths that contribute to the anti-helminth response.
{"title":"Intestinal tuft cells: weep, sweep … secrete","authors":"Kirsty Minton","doi":"10.1038/s41577-024-01052-2","DOIUrl":"10.1038/s41577-024-01052-2","url":null,"abstract":"Two papers in Immunity report the effects of acetylcholine secretion by intestinal tuft cells on epithelial cells and helminths that contribute to the anti-helminth response.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093584","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 : 2024-05-23DOI: 10.1038/s41577-024-01047-z
Sandra Nakandakari-Higa
In this Tools of the Trade article, Sandra Nakandakari-Higa (of the Gabriel Victora lab) describes the latest version of their LIPSTIC technique for tracking diverse cell–cell interactions in vivo.
{"title":"Universal LIPSTIC: a new tool for decoding cellular interactions","authors":"Sandra Nakandakari-Higa","doi":"10.1038/s41577-024-01047-z","DOIUrl":"10.1038/s41577-024-01047-z","url":null,"abstract":"In this Tools of the Trade article, Sandra Nakandakari-Higa (of the Gabriel Victora lab) describes the latest version of their LIPSTIC technique for tracking diverse cell–cell interactions in vivo.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085467","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 : 2024-05-14DOI: 10.1038/s41577-024-01046-0
Alexandra Flemming
{"title":"Time of day determines cancer immunotherapy response","authors":"Alexandra Flemming","doi":"10.1038/s41577-024-01046-0","DOIUrl":"10.1038/s41577-024-01046-0","url":null,"abstract":"","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919749","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 : 2024-05-08DOI: 10.1038/s41577-024-01042-4
Yvonne Bordon
Commensal bacteria induce liver macrophages that protect the tissue against inflammation.
共生细菌诱导肝脏巨噬细胞，保护组织免受炎症侵袭。
{"title":"Protect the periportals","authors":"Yvonne Bordon","doi":"10.1038/s41577-024-01042-4","DOIUrl":"10.1038/s41577-024-01042-4","url":null,"abstract":"Commensal bacteria induce liver macrophages that protect the tissue against inflammation.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881284","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 : 2024-05-07DOI: 10.1038/s41577-024-01025-5
Iain Comerford, Shaun R. McColl
Leukocyte migration is a fundamental component of innate and adaptive immune responses as it governs the recruitment and localization of these motile cells, which is crucial for immune cell priming, effector functions, memory responses and immune regulation. This complex cellular trafficking system is controlled to a large extent via highly regulated production of secreted chemokines and the restricted expression of their membrane-tethered G-protein-coupled receptors. The activity of chemokines and their receptors is also regulated by a subfamily of molecules known as atypical chemokine receptors (ACKRs), which are chemokine receptor-like molecules that do not couple to the classical signalling pathways that promote cell migration in response to chemokine ligation. There has been a great deal of progress in understanding the biology of these receptors and their functions in the immune system in the past decade. Here, we describe the contribution of the various ACKRs to innate and adaptive immune responses, focussing specifically on recent progress. This includes recent findings that have defined the role for ACKRs in sculpting extracellular chemokine gradients, findings that broaden the spectrum of chemokine ligands recognized by these receptors, candidate new additions to ACKR family, and our increasing understanding of the role of these receptors in shaping the migration of innate and adaptive immune cells. This Review from Comerford and McColl discusses recent advances that have been made in understanding the biology of the atypical chemokine receptor (ACKR) family. The authors explain how these receptors interact with their ligands to shape immune responses and also highlight potential new additions to the ACKR family.
白细胞迁移是先天性和适应性免疫反应的基本组成部分，因为它控制着这些运动细胞的招募和定位，这对免疫细胞的启动、效应功能、记忆反应和免疫调节至关重要。这种复杂的细胞运输系统在很大程度上是通过高度调节分泌型趋化因子的产生及其膜系 G 蛋白偶联受体的限制性表达来控制的。趋化因子及其受体的活性还受一个被称为非典型趋化因子受体（ACKRs）的分子亚家族的调控，ACKRs 是类似于趋化因子受体的分子，不与经典的信号通路耦合，这些信号通路在趋化因子的作用下促进细胞迁移。在过去十年中，人们在了解这些受体的生物学特性及其在免疫系统中的功能方面取得了很大进展。在这里，我们描述了各种 ACKR 对先天性和适应性免疫反应的贡献，并特别关注最近的进展。这包括最近确定 ACKR 在形成细胞外趋化因子梯度中的作用的研究结果、扩大这些受体识别的趋化因子配体范围的研究结果、ACKR 家族的候选新成员，以及我们对这些受体在形成先天性和适应性免疫细胞迁移中的作用的进一步了解。
{"title":"Atypical chemokine receptors in the immune system","authors":"Iain Comerford, Shaun R. McColl","doi":"10.1038/s41577-024-01025-5","DOIUrl":"10.1038/s41577-024-01025-5","url":null,"abstract":"Leukocyte migration is a fundamental component of innate and adaptive immune responses as it governs the recruitment and localization of these motile cells, which is crucial for immune cell priming, effector functions, memory responses and immune regulation. This complex cellular trafficking system is controlled to a large extent via highly regulated production of secreted chemokines and the restricted expression of their membrane-tethered G-protein-coupled receptors. The activity of chemokines and their receptors is also regulated by a subfamily of molecules known as atypical chemokine receptors (ACKRs), which are chemokine receptor-like molecules that do not couple to the classical signalling pathways that promote cell migration in response to chemokine ligation. There has been a great deal of progress in understanding the biology of these receptors and their functions in the immune system in the past decade. Here, we describe the contribution of the various ACKRs to innate and adaptive immune responses, focussing specifically on recent progress. This includes recent findings that have defined the role for ACKRs in sculpting extracellular chemokine gradients, findings that broaden the spectrum of chemokine ligands recognized by these receptors, candidate new additions to ACKR family, and our increasing understanding of the role of these receptors in shaping the migration of innate and adaptive immune cells. This Review from Comerford and McColl discusses recent advances that have been made in understanding the biology of the atypical chemokine receptor (ACKR) family. The authors explain how these receptors interact with their ligands to shape immune responses and also highlight potential new additions to the ACKR family.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845450","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 : 2024-05-02DOI: 10.1038/s41577-024-01029-1
Thi H. O. Nguyen, Louise C. Rowntree, Brendon Y. Chua, Ryan S. Thwaites, Katherine Kedzierska
Influenza A viruses remain a global threat to human health, with continued pandemic potential. In this Review, we discuss our current understanding of the optimal immune responses that drive recovery from influenza virus infection, highlighting the fine balance between protective immune mechanisms and detrimental immunopathology. We describe the contribution of innate and adaptive immune cells, inflammatory modulators and antibodies to influenza virus-specific immunity, inflammation and immunopathology. We highlight recent human influenza virus challenge studies that advance our understanding of susceptibility to influenza and determinants of symptomatic disease. We also describe studies of influenza virus-specific immunity in high-risk groups following infection and vaccination that inform the design of future vaccines to promote optimal antiviral immunity, particularly in vulnerable populations. Finally, we draw on lessons from the COVID-19 pandemic to refocus our attention to the ever-changing, highly mutable influenza A virus, predicted to cause future global pandemics. An optimal immune response to influenza virus strikes a balance between protective antiviral immune mechanisms and detrimental immunopathology. Here, the authors review the immune mechanisms responsible for each side of this balance and how this may inform future vaccine design.
{"title":"Defining the balance between optimal immunity and immunopathology in influenza virus infection","authors":"Thi H. O. Nguyen, Louise C. Rowntree, Brendon Y. Chua, Ryan S. Thwaites, Katherine Kedzierska","doi":"10.1038/s41577-024-01029-1","DOIUrl":"10.1038/s41577-024-01029-1","url":null,"abstract":"Influenza A viruses remain a global threat to human health, with continued pandemic potential. In this Review, we discuss our current understanding of the optimal immune responses that drive recovery from influenza virus infection, highlighting the fine balance between protective immune mechanisms and detrimental immunopathology. We describe the contribution of innate and adaptive immune cells, inflammatory modulators and antibodies to influenza virus-specific immunity, inflammation and immunopathology. We highlight recent human influenza virus challenge studies that advance our understanding of susceptibility to influenza and determinants of symptomatic disease. We also describe studies of influenza virus-specific immunity in high-risk groups following infection and vaccination that inform the design of future vaccines to promote optimal antiviral immunity, particularly in vulnerable populations. Finally, we draw on lessons from the COVID-19 pandemic to refocus our attention to the ever-changing, highly mutable influenza A virus, predicted to cause future global pandemics. An optimal immune response to influenza virus strikes a balance between protective antiviral immune mechanisms and detrimental immunopathology. Here, the authors review the immune mechanisms responsible for each side of this balance and how this may inform future vaccine design.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821097","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 : 2024-05-02DOI: 10.1038/s41577-024-01030-8
Tim R. Mosmann, Andrew J. McMichael, Alexandre LeVert, John W. McCauley, Jeffrey W. Almond
Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts. Compared with many other vaccines, current vaccines against influenza provide only limited protection. Here, the authors describe the challenges and recent attempts at generating T cell-based vaccines. It may be important to combine T cell-based vaccines with antibody-based vaccines to provide long-lasting immunity across influenza virus strains.
疫苗接种仍然是我们抵御流感的主要手段，流感每年造成大量死亡，并构成严重的大流行威胁。流感病毒通过迅速改变其表面抗原来逃避免疫，但即使疫苗与当前流行的病毒株非常匹配，流感疫苗也不如许多其他疫苗有效。流感疫苗的研发历来侧重于诱导保护性抗体，但越来越多的证据表明，T 细胞反应也对流感有保护作用。因此，未来旨在促进广泛的 T 细胞效应功能和抗体的疫苗可能会提供更强的保护。正如我们所讨论的，这类疫苗面临着一些挑战，需要新的战略和经济考量。疫苗诱导的与保护相关的 T 细胞可能存在于肺部或淋巴组织中，因此需要更多侵入性试验来评估候选疫苗的免疫原性。T 细胞功能可能会抑制和化解感染，而不是完全预防感染和早期疾病，这就要求根据预防严重疾病和死亡而不是无症状感染来评估疫苗的有效性。对 T 细胞反应和不常见的临床结果进行测量既复杂又昂贵，因此出于经济原因，需要对临床试验设计进行创新。尽管如此，为了实现更有效的流感疫苗这一目标，我们有理由继续加紧努力。
{"title":"Opportunities and challenges for T cell-based influenza vaccines","authors":"Tim R. Mosmann, Andrew J. McMichael, Alexandre LeVert, John W. McCauley, Jeffrey W. Almond","doi":"10.1038/s41577-024-01030-8","DOIUrl":"10.1038/s41577-024-01030-8","url":null,"abstract":"Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts. Compared with many other vaccines, current vaccines against influenza provide only limited protection. Here, the authors describe the challenges and recent attempts at generating T cell-based vaccines. It may be important to combine T cell-based vaccines with antibody-based vaccines to provide long-lasting immunity across influenza virus strains.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819429","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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