Pub Date : 2024-06-19DOI: 10.1016/j.immuni.2024.05.024
Kelly A. Hagadorn, Mary E. Peterson, Hemanta Kole, Bethany Scott, Jeff Skinner, Ababacar Diouf, Eizo Takashima, Aissata Ongoiba, Safiatou Doumbo, Didier Doumtabe, Shanping Li, Padmapriya Sekar, Mei Yan, Chengsong Zhu, Hikaru Nagaoka, Bernard N. Kanoi, Quan-Zhen Li, Carole Long, Eric O. Long, Kassoum Kayentao, Christine S. Hopp
Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.
{"title":"Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria","authors":"Kelly A. Hagadorn, Mary E. Peterson, Hemanta Kole, Bethany Scott, Jeff Skinner, Ababacar Diouf, Eizo Takashima, Aissata Ongoiba, Safiatou Doumbo, Didier Doumtabe, Shanping Li, Padmapriya Sekar, Mei Yan, Chengsong Zhu, Hikaru Nagaoka, Bernard N. Kanoi, Quan-Zhen Li, Carole Long, Eric O. Long, Kassoum Kayentao, Christine S. Hopp","doi":"10.1016/j.immuni.2024.05.024","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.024","url":null,"abstract":"<p>Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (<em>n</em> = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic <em>Plasmodium falciparum</em> infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind <em>P. falciparum</em> proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425200","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 : 2024-06-18DOI: 10.1016/j.immuni.2024.05.023
Oliver T. Burton, Orian Bricard, Samar Tareen, Vaclav Gergelits, Simon Andrews, Laura Biggins, Carlos P. Roca, Carly Whyte, Steffie Junius, Aleksandra Brajic, Emanuela Pasciuto, Magda Ali, Pierre Lemaitre, Susan M. Schlenner, Harumichi Ishigame, Brian D. Brown, James Dooley, Adrian Liston
The tissues are the site of many important immunological reactions, yet how the immune system is controlled at these sites remains opaque. Recent studies have identified Foxp3+ regulatory T (Treg) cells in non-lymphoid tissues with unique characteristics compared with lymphoid Treg cells. However, tissue Treg cells have not been considered holistically across tissues. Here, we performed a systematic analysis of the Treg cell population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency, and common molecular dependencies. Tissue Treg cells from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg cell entry and were tissue-agnostic on tissue homing. Together, these results demonstrate that the tissue-resident Treg cell pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Treg cells, characterized by transient multi-tissue migration. This work suggests common regulatory mechanisms may allow pan-tissue Treg cells to safeguard homeostasis across the body.
{"title":"The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program","authors":"Oliver T. Burton, Orian Bricard, Samar Tareen, Vaclav Gergelits, Simon Andrews, Laura Biggins, Carlos P. Roca, Carly Whyte, Steffie Junius, Aleksandra Brajic, Emanuela Pasciuto, Magda Ali, Pierre Lemaitre, Susan M. Schlenner, Harumichi Ishigame, Brian D. Brown, James Dooley, Adrian Liston","doi":"10.1016/j.immuni.2024.05.023","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.023","url":null,"abstract":"<p>The tissues are the site of many important immunological reactions, yet how the immune system is controlled at these sites remains opaque. Recent studies have identified Foxp3<sup>+</sup> regulatory T (Treg) cells in non-lymphoid tissues with unique characteristics compared with lymphoid Treg cells. However, tissue Treg cells have not been considered holistically across tissues. Here, we performed a systematic analysis of the Treg cell population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency, and common molecular dependencies. Tissue Treg cells from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg cell entry and were tissue-agnostic on tissue homing. Together, these results demonstrate that the tissue-resident Treg cell pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Treg cells, characterized by transient multi-tissue migration. This work suggests common regulatory mechanisms may allow pan-tissue Treg cells to safeguard homeostasis across the body.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334527","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}
Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.
转录调节因子ZFP318在生殖中心(GC)出苗期记忆B细胞前体和记忆B细胞(MBC)中被诱导表达。我们使用一种条件性 ZFP318 荧光报告器(该报告器也能消融 ZFP318 表达的细胞)发现,ZFP318 表达的 MBCs 高度富集于 GC 派生细胞中。虽然ZFP318表达的MBC只占抗原特异性MBC区系的少数,但它们的消减严重影响了回忆反应。Zfp318的缺失不会改变初级反应的程度,但会显著降低MBC参与回忆反应的程度。CD40 结扎可促进 Zfp318 的表达,而 B 细胞受体(BCR)信号转导则具有抑制作用。ZFP318的强制表达提高了MBC的回忆能力,否则它们的反应能力会很差。ZFP318缺陷的MBC表达的线粒体基因较少,线粒体结构受损,易受再激活诱导的细胞死亡影响。表达 ZFP318 的 MBC 的丰度(而不是抗原特异性 MBC 的数量)与原素增强疫苗的效力相关。因此,ZFP318控制着MBC的可召回性,是体液免疫记忆的质量检查点。
{"title":"High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function","authors":"Yifeng Wang, Wen Shao, Xin Liu, Qingtai Liang, Jiaqi Lei, Wenjuan Shi, Miao Mei, Ying Li, Xu Tan, Guocan Yu, Li Yu, Linqi Zhang, Hai Qi","doi":"10.1016/j.immuni.2024.05.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.022","url":null,"abstract":"<p>Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of <em>Zfp318</em> did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted <em>Zfp318</em> expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333819","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 : 2024-06-13DOI: 10.1016/j.immuni.2024.05.019
Nadège Nziza, Wonyeong Jung, Maanasa Mendu, Tina Chen, Boris Julg, Barney Graham, Octavio Ramilo, Asuncion Mejias, Galit Alter
Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection (LRTI) and hospitalization in infants. However, the mechanisms of immune control in infants remain incompletely understood. Antibody profiling against attachment (G) and fusion (F) proteins in children less than 2 years of age, with mild (outpatients) or severe (inpatients) RSV disease, indicated substantial age-dependent differences in RSV-specific immunity. Maternal antibodies were detectable for the first 3 months of life, followed by a long window of immune vulnerability between 3 and 6 months and a rapid evolution of FcγR-recruiting immunity after 6 months of age. Acutely ill hospitalized children exhibited lower G-specific antibodies compared with healthy controls. With disease resolution, RSV-infected infants generated broad functional RSV strain-specific G-responses and evolved cross-reactive F-responses, with minimal maternal imprinting. These data suggest an age-independent RSV G-specific functional humoral correlate of protection, and the evolution of RSV F-specific functional immunity with disease resolution.
呼吸道合胞病毒(RSV)是导致婴儿下呼吸道感染(LRTI)和住院治疗的最常见原因之一。然而,人们对婴儿的免疫控制机制仍不甚了解。对患有轻度(门诊病人)或重度(住院病人)RSV 疾病的 2 岁以下儿童进行的附着蛋白(G)和融合蛋白(F)抗体分析表明,RSV 特异性免疫力存在很大的年龄差异。出生后的头 3 个月可以检测到母体抗体,3 到 6 个月之间会出现较长的免疫脆弱期,6 个月后 FcγR 招募免疫会迅速发展。与健康对照组相比,急性病住院儿童的 G 特异性抗体较低。随着疾病的缓解,RSV 感染婴儿产生了广泛的功能性 RSV 株系特异性 G 反应,并进化出了交叉反应性 F 反应,母体印记极小。这些数据表明,RSV G 特异性功能性体液保护与年龄无关,随着疾病的缓解,RSV F 特异性功能性免疫也会发生演变。
{"title":"Longitudinal humoral analysis in RSV-infected infants identifies pre-existing RSV strain-specific G and evolving cross-reactive F antibodies","authors":"Nadège Nziza, Wonyeong Jung, Maanasa Mendu, Tina Chen, Boris Julg, Barney Graham, Octavio Ramilo, Asuncion Mejias, Galit Alter","doi":"10.1016/j.immuni.2024.05.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.019","url":null,"abstract":"<p>Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection (LRTI) and hospitalization in infants. However, the mechanisms of immune control in infants remain incompletely understood. Antibody profiling against attachment (G) and fusion (F) proteins in children less than 2 years of age, with mild (outpatients) or severe (inpatients) RSV disease, indicated substantial age-dependent differences in RSV-specific immunity. Maternal antibodies were detectable for the first 3 months of life, followed by a long window of immune vulnerability between 3 and 6 months and a rapid evolution of FcγR-recruiting immunity after 6 months of age. Acutely ill hospitalized children exhibited lower G-specific antibodies compared with healthy controls. With disease resolution, RSV-infected infants generated broad functional RSV strain-specific G-responses and evolved cross-reactive F-responses, with minimal maternal imprinting. These data suggest an age-independent RSV G-specific functional humoral correlate of protection, and the evolution of RSV F-specific functional immunity with disease resolution.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315884","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 : 2024-06-13DOI: 10.1016/j.immuni.2024.05.018
Albert C. Yeh, Motoko Koyama, Olivia G. Waltner, Simone A. Minnie, Julie R. Boiko, Tamer B. Shabaneh, Shuichiro Takahashi, Ping Zhang, Kathleen S. Ensbey, Christine R. Schmidt, Samuel R.W. Legg, Tomoko Sekiguchi, Ethan Nelson, Shruti S. Bhise, Andrew R. Stevens, Tracy Goodpaster, Saranya Chakka, Scott N. Furlan, Kate A. Markey, Marie E. Bleakley, Geoffrey R. Hill
Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.
同种异体 T 细胞扩增是移植物抗宿主病(GVHD)的主要决定因素,目前的理论认为这是由于供体和受体之间组织相容性抗原的差异造成的。这种模式代表了一个封闭的遗传系统,在这个系统中,供体 T 细胞与多肽-主要组织相容性复合物(MHC)相互作用,但由于 T 细胞库稀少,克隆检测仍具有挑战性。我们利用小鼠干细胞移植系统中的供体和受体T细胞受体(TCR)频率建立了贝叶斯模型,以确定基因相同的供体-受体配对中T细胞克隆的有限共同扩增。供体CD4+ T细胞克隆亚型在完全相同的受体中不同程度地扩增,并且依赖微生物群。微生物群特异性T细胞提高了GVHD致死率,并能在异体反应过程中靶向胃肠上皮呈现的微生物抗原。微生物群是同源抗原的来源,有助于克隆型T细胞扩增和诱导GVHD,与供体-受体遗传无关。
{"title":"Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation","authors":"Albert C. Yeh, Motoko Koyama, Olivia G. Waltner, Simone A. Minnie, Julie R. Boiko, Tamer B. Shabaneh, Shuichiro Takahashi, Ping Zhang, Kathleen S. Ensbey, Christine R. Schmidt, Samuel R.W. Legg, Tomoko Sekiguchi, Ethan Nelson, Shruti S. Bhise, Andrew R. Stevens, Tracy Goodpaster, Saranya Chakka, Scott N. Furlan, Kate A. Markey, Marie E. Bleakley, Geoffrey R. Hill","doi":"10.1016/j.immuni.2024.05.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.018","url":null,"abstract":"<p>Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4<sup>+</sup> T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315816","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 : 2024-06-11DOI: 10.1016/j.immuni.2024.05.013
Aleksandra Deczkowska
Phagocytic microglia such as proliferative region-associated microglia and disease-associated microglia appear in the brain transiently during development and across various brain pathologies, but their function and degree of plasticity remain unclear. In this issue of Immunity, Barclay et al. established a novel Clec7a-CreERT2 mouse line to uncover the plasticity of this cell state and its role in a model of myelin injury.
{"title":"Not so aDAMant after all: Plasticity of phagocytic microglia","authors":"Aleksandra Deczkowska","doi":"10.1016/j.immuni.2024.05.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.013","url":null,"abstract":"<p>Phagocytic microglia such as proliferative region-associated microglia and disease-associated microglia appear in the brain transiently during development and across various brain pathologies, but their function and degree of plasticity remain unclear. In this issue of <em>Immunity</em>, Barclay et al. established a novel Clec7a-CreER<sup>T2</sup> mouse line to uncover the plasticity of this cell state and its role in a model of myelin injury.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304661","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 : 2024-06-11DOI: 10.1016/j.immuni.2024.05.016
Ronald N. Germain, Eliezer M. Van Allen, Gosia Trynka, John S. Tsang, Dominic Grün, Ashley L. Kiemen, Yigong Shi, Aimee Pugh Bernard, Garry P. Nolan
AI is rapidly becoming part of many aspects of daily life, with an impact that reaches all fields of research. We asked investigators to share their thoughts on how AI is changing immunology research, what is necessary to move forward, the potential and the pitfalls, and what will remain unchanged as the field journeys into a new era.
{"title":"AI and immunology","authors":"Ronald N. Germain, Eliezer M. Van Allen, Gosia Trynka, John S. Tsang, Dominic Grün, Ashley L. Kiemen, Yigong Shi, Aimee Pugh Bernard, Garry P. Nolan","doi":"10.1016/j.immuni.2024.05.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.016","url":null,"abstract":"<p>AI is rapidly becoming part of many aspects of daily life, with an impact that reaches all fields of research. We asked investigators to share their thoughts on how AI is changing immunology research, what is necessary to move forward, the potential and the pitfalls, and what will remain unchanged as the field journeys into a new era.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304682","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 : 2024-06-11DOI: 10.1016/j.immuni.2024.05.011
Johanna Kotrba, Anne Dudeck
Mast cells (MCs) are effectors in type 2 immunity, well known for their detrimental roles in allergy. In this issue of Immunity, Alhallak et al. now identify a protective role of MCs against exacerbated immune responses mediated by prostaglandin E2 (PGE2)-driven soluble ST2.
{"title":"Mast cells: The Janus of type 2 inflammation","authors":"Johanna Kotrba, Anne Dudeck","doi":"10.1016/j.immuni.2024.05.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.011","url":null,"abstract":"<p>Mast cells (MCs) are effectors in type 2 immunity, well known for their detrimental roles in allergy. In this issue of <em>Immunity</em>, Alhallak et al. now identify a protective role of MCs against exacerbated immune responses mediated by prostaglandin E<sub>2</sub> (PGE<sub>2</sub>)-driven soluble ST2.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304729","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 : 2024-06-11Epub Date: 2024-05-21DOI: 10.1016/j.immuni.2024.04.026
Willem Van Der Byl, Simone Nüssing, Timothy J Peters, Antonio Ahn, Hanjie Li, Guy Ledergor, Eyal David, Andrew S Koh, Mayura V Wagle, Christian Deo T Deguit, Maria N de Menezes, Avraham Travers, Shienny Sampurno, Kelly M Ramsbottom, Rui Li, Axel Kallies, Paul A Beavis, Ralf Jungmann, Maartje M C Bastings, Gabrielle T Belz, Shom Goel, Joseph A Trapani, Gerald R Crabtree, Howard Y Chang, Ido Amit, Chris C Goodnow, Fabio Luciani, Ian A Parish
Peripheral CD8+ T cell tolerance is a checkpoint in both autoimmune disease and anti-cancer immunity. Despite its importance, the relationship between tolerance-induced states and other CD8+ T cell differentiation states remains unclear. Using flow cytometric phenotyping, single-cell RNA sequencing (scRNA-seq), and chromatin accessibility profiling, we demonstrated that in vivo peripheral tolerance to a self-antigen triggered a fundamentally distinct differentiation state separate from exhaustion, memory, and functional effector cells but analogous to cells defectively primed against tumors. Tolerant cells diverged early and progressively from effector cells, adopting a transcriptionally and epigenetically distinct state within 60 h of antigen encounter. Breaching tolerance required the synergistic actions of strong T cell receptor (TCR) signaling and inflammation, which cooperatively induced gene modules that enhanced protein translation. Weak TCR signaling during bystander infection failed to breach tolerance due to the uncoupling of effector gene expression from protein translation. Thus, tolerance engages a distinct differentiation trajectory enforced by protein translation defects.
外周 CD8+ T 细胞耐受是自身免疫性疾病和抗癌免疫的一个检查点。尽管它很重要,但耐受诱导状态与其他 CD8+ T 细胞分化状态之间的关系仍不清楚。利用流式细胞表型分析、单细胞 RNA 测序(scRNA-seq)和染色质可及性分析,我们证明了体内外周对自身抗原的耐受引发了一种根本不同的分化状态,这种状态与衰竭、记忆和功能效应细胞不同,但类似于针对肿瘤的缺陷细胞。耐受细胞很早就与效应细胞逐渐分化,在遇到抗原后的60小时内采用了转录和表观遗传学上的独特状态。打破耐受性需要强大的T细胞受体(TCR)信号和炎症的协同作用,它们共同诱导基因模块,增强蛋白质翻译。由于效应基因表达与蛋白质翻译脱钩,旁观者感染期间的弱TCR信号不能突破耐受性。因此,耐受性涉及一个由蛋白质翻译缺陷强化的独特分化轨迹。
{"title":"The CD8<sup>+</sup> T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.","authors":"Willem Van Der Byl, Simone Nüssing, Timothy J Peters, Antonio Ahn, Hanjie Li, Guy Ledergor, Eyal David, Andrew S Koh, Mayura V Wagle, Christian Deo T Deguit, Maria N de Menezes, Avraham Travers, Shienny Sampurno, Kelly M Ramsbottom, Rui Li, Axel Kallies, Paul A Beavis, Ralf Jungmann, Maartje M C Bastings, Gabrielle T Belz, Shom Goel, Joseph A Trapani, Gerald R Crabtree, Howard Y Chang, Ido Amit, Chris C Goodnow, Fabio Luciani, Ian A Parish","doi":"10.1016/j.immuni.2024.04.026","DOIUrl":"10.1016/j.immuni.2024.04.026","url":null,"abstract":"<p><p>Peripheral CD8<sup>+</sup> T cell tolerance is a checkpoint in both autoimmune disease and anti-cancer immunity. Despite its importance, the relationship between tolerance-induced states and other CD8<sup>+</sup> T cell differentiation states remains unclear. Using flow cytometric phenotyping, single-cell RNA sequencing (scRNA-seq), and chromatin accessibility profiling, we demonstrated that in vivo peripheral tolerance to a self-antigen triggered a fundamentally distinct differentiation state separate from exhaustion, memory, and functional effector cells but analogous to cells defectively primed against tumors. Tolerant cells diverged early and progressively from effector cells, adopting a transcriptionally and epigenetically distinct state within 60 h of antigen encounter. Breaching tolerance required the synergistic actions of strong T cell receptor (TCR) signaling and inflammation, which cooperatively induced gene modules that enhanced protein translation. Weak TCR signaling during bystander infection failed to breach tolerance due to the uncoupling of effector gene expression from protein translation. Thus, tolerance engages a distinct differentiation trajectory enforced by protein translation defects.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081271","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 : 2024-06-11DOI: 10.1016/j.immuni.2024.05.010
Rebecca E. Hamlin, Catherine A. Blish
Long COVID (LC) is a condition in which patients do not fully recover from the initial SARS-CoV-2 infection but rather have persistent or new symptoms for months to years following the infection. Ongoing research efforts are investigating the pathophysiologic mechanisms of LC and exploring preventative and therapeutic treatment approaches for patients. As a burgeoning area of investigation, LC research can be structured to be more inclusive, innovative, and effective. In this perspective, we highlight opportunities for patient engagement and diverse research expertise, as well as the challenges of developing definitions and reproducible studies. Our intention is to provide a foundation for collaboration and progress in understanding the biomarkers and mechanisms driving LC.
{"title":"Challenges and opportunities in long COVID research","authors":"Rebecca E. Hamlin, Catherine A. Blish","doi":"10.1016/j.immuni.2024.05.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.010","url":null,"abstract":"<p>Long COVID (LC) is a condition in which patients do not fully recover from the initial SARS-CoV-2 infection but rather have persistent or new symptoms for months to years following the infection. Ongoing research efforts are investigating the pathophysiologic mechanisms of LC and exploring preventative and therapeutic treatment approaches for patients. As a burgeoning area of investigation, LC research can be structured to be more inclusive, innovative, and effective. In this perspective, we highlight opportunities for patient engagement and diverse research expertise, as well as the challenges of developing definitions and reproducible studies. Our intention is to provide a foundation for collaboration and progress in understanding the biomarkers and mechanisms driving LC.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304644","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}