Pub Date : 2025-01-15DOI: 10.1016/j.immuni.2025.01.001
Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, JoAnne L. Flynn
(Immunity 57, 2380–2398.e1–e6; October 8, 2024)
(免疫57,2380-2398.e1-e6；2024年10月8日)
{"title":"CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection","authors":"Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, JoAnne L. Flynn","doi":"10.1016/j.immuni.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.001","url":null,"abstract":"(Immunity <em>57</em>, 2380–2398.e1–e6; October 8, 2024)","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"24 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987029","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 : 2025-01-15DOI: 10.1016/j.immuni.2024.12.011
Clara Young, Mandeep Singh, Katherine J.L. Jackson, Matt A. Field, Timothy J. Peters, Stefano Angioletti-Uberti, Daan Frenkel, Shyamsundar Ravishankar, Money Gupta, Jing J. Wang, David Agapiou, Megan L. Faulks, Ghamdan Al-Eryani, Fabio Luciani, Tom P. Gordon, Joanne H. Reed, Mark Danta, Andrew Carr, Anthony D. Kelleher, Gregory J. Dore, Christopher C. Goodnow
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen. Whole-genome sequencing revealed thousands of somatic mutations, numerically comparable to chronic lymphocytic leukemia and normal memory B cells, but with 1–2 corresponding to driver mutations found recurrently in B cell leukemia and lymphoma. V(D)J hypermutation created autoantibodies with compromised solubility in complex with self-IgG. In this virus-induced autoimmune disease, infection promotes a catastrophic confluence of somatic mutagenesis in the descendants of a single B cell.
{"title":"A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease","authors":"Clara Young, Mandeep Singh, Katherine J.L. Jackson, Matt A. Field, Timothy J. Peters, Stefano Angioletti-Uberti, Daan Frenkel, Shyamsundar Ravishankar, Money Gupta, Jing J. Wang, David Agapiou, Megan L. Faulks, Ghamdan Al-Eryani, Fabio Luciani, Tom P. Gordon, Joanne H. Reed, Mark Danta, Andrew Carr, Anthony D. Kelleher, Gregory J. Dore, Christopher C. Goodnow","doi":"10.1016/j.immuni.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.011","url":null,"abstract":"The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen. Whole-genome sequencing revealed thousands of somatic mutations, numerically comparable to chronic lymphocytic leukemia and normal memory B cells, but with 1–2 corresponding to driver mutations found recurrently in B cell leukemia and lymphoma. V(D)J hypermutation created autoantibodies with compromised solubility in complex with self-IgG. In this virus-induced autoimmune disease, infection promotes a catastrophic confluence of somatic mutagenesis in the descendants of a single B cell.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"118 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981690","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}
Mitochondria play critical roles in intrinsic apoptosis and NLRP3 inflammasome activation, but how these processes are interconnected remains unclear. In this issue of Immunity, Saller et al. unveiled the complexity of NLRP3 activators, highlighting mitochondria’s roles in switching apoptosis to NLRP3 inflammasome activation.
{"title":"Mitochondria and NLRP3: To die or inflame","authors":"Shuangshuang Yang, Guannan Huang, Jenny P.-Y. Ting","doi":"10.1016/j.immuni.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.007","url":null,"abstract":"Mitochondria play critical roles in intrinsic apoptosis and NLRP3 inflammasome activation, but how these processes are interconnected remains unclear. In this issue of <em>Immunity</em>, Saller et al. unveiled the complexity of NLRP3 activators, highlighting mitochondria’s roles in switching apoptosis to NLRP3 inflammasome activation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"29 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974586","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.11.022
Ruodi Yang, Danyang He
Immune activation during sustained stress typically worsens stress-related psychopathology. Whether it can enhance stress resilience remains unclear. In this issue of Immunity, Xia, Lu, Lan et al.1 uncover an anxiolytic function of intestinal IL-22 pathway, which protects against psychological stress.
{"title":"Gut know-how: IL-22 from T cells boosts stress resilience","authors":"Ruodi Yang, Danyang He","doi":"10.1016/j.immuni.2024.11.022","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.022","url":null,"abstract":"Immune activation during sustained stress typically worsens stress-related psychopathology. Whether it can enhance stress resilience remains unclear. In this issue of <em>Immunity</em>, Xia, Lu, Lan et al.<span><span><sup>1</sup></span></span> uncover an anxiolytic function of intestinal IL-22 pathway, which protects against psychological stress.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"14 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974587","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.12.005
Matthew C. Sinton, Olivia Shorthouse, Alice Costain, Juan F. Quintana
Interleukin-17 plays a major role in controlling adipose tissue homeostasis. In a recent study published in Nature, Douglas et al. demonstrate that time-of-day-dependent expression of interleukin-17 by tissue-resident innate lymphocytes in the adipose tissue drives circadian regulation of adipose tissue homeostasis and function.
{"title":"Interleukin-17 and fat: Timing is everything","authors":"Matthew C. Sinton, Olivia Shorthouse, Alice Costain, Juan F. Quintana","doi":"10.1016/j.immuni.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.005","url":null,"abstract":"Interleukin-17 plays a major role in controlling adipose tissue homeostasis. In a recent study published in <em>Nature</em>, Douglas et al. demonstrate that time-of-day-dependent expression of interleukin-17 by tissue-resident innate lymphocytes in the adipose tissue drives circadian regulation of adipose tissue homeostasis and function.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"16 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974588","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.12.010
Fernando Fernández-García, Barbara B. Maier
Inhibiting T cell exhaustion is an attractive cancer immunotherapy strategy. In this issue of Immunity, Waibl Polania et al. examine the microenvironmental signals regulating terminal T cell exhaustion and find that antigen presentation by tumor-associated macrophages, not tumor cells, drives terminal T cell exhaustion in glioblastoma.
抑制 T 细胞衰竭是一种极具吸引力的癌症免疫疗法策略。在本期《免疫》杂志上，Waibl Polania 等人研究了调控终末 T 细胞衰竭的微环境信号，发现在胶质母细胞瘤中，是肿瘤相关巨噬细胞而非肿瘤细胞的抗原呈递驱动了终末 T 细胞衰竭。
{"title":"Restimulation by macrophages exhausts T cells","authors":"Fernando Fernández-García, Barbara B. Maier","doi":"10.1016/j.immuni.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.010","url":null,"abstract":"Inhibiting T cell exhaustion is an attractive cancer immunotherapy strategy. In this issue of <em>Immunity</em>, Waibl Polania et al. examine the microenvironmental signals regulating terminal T cell exhaustion and find that antigen presentation by tumor-associated macrophages, not tumor cells, drives terminal T cell exhaustion in glioblastoma.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"75 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974589","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.12.001
Lukasz Kedzierski, Katherine Kedzierska
The mechanisms underpinning susceptibility to influenza virus infection, resulting in life-threatening disease, are not well understood. In this issue of Immunity, Chakraborty et al. demonstrate that sialylated IgG suppresses NF-κB-driven inflammatory responses in the lungs by inducing repressor element-1 silencing transcription factor (REST) to prevent excessive inflammation without impacting viral replication.
{"title":"IgG sialylation puts lung inflammation to REST","authors":"Lukasz Kedzierski, Katherine Kedzierska","doi":"10.1016/j.immuni.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.001","url":null,"abstract":"The mechanisms underpinning susceptibility to influenza virus infection, resulting in life-threatening disease, are not well understood. In this issue of <em>Immunity</em>, Chakraborty et al. demonstrate that sialylated IgG suppresses NF-κB-driven inflammatory responses in the lungs by inducing repressor element-1 silencing transcription factor (REST) to prevent excessive inflammation without impacting viral replication.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"90 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974651","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.12.009
Melissa Ng, Daniela Cerezo-Wallis, Lai Guan Ng, Andres Hidalgo
There is a renewed interest in neutrophil biology, largely instigated by their prominence in cancer. From an immunologist’s perspective, a conceptual breakthrough is the realization that prototypical inflammatory, cytotoxic leukocytes can be tamed to promote the survival and growth of other cells. This has sparked interest in defining the biological principles and molecular mechanisms driving the adaptation of neutrophils to cancer. Yet, many questions remain: is this adaptation mediated by reprogramming mature neutrophils inside the tumoral mass, or rather by rewiring granulopoiesis in the bone marrow? Why, in some instances, are neutrophils beneficial and in others detrimental to cancer? How many different functional programs can be induced in neutrophils by tumors, and is this dependent on the type of tumor? This review summarizes what we know about these questions and discusses therapeutic strategies based on our incipient knowledge of how neutrophils adapt to cancer.
{"title":"Adaptations of neutrophils in cancer","authors":"Melissa Ng, Daniela Cerezo-Wallis, Lai Guan Ng, Andres Hidalgo","doi":"10.1016/j.immuni.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.009","url":null,"abstract":"There is a renewed interest in neutrophil biology, largely instigated by their prominence in cancer. From an immunologist’s perspective, a conceptual breakthrough is the realization that prototypical inflammatory, cytotoxic leukocytes can be tamed to promote the survival and growth of other cells. This has sparked interest in defining the biological principles and molecular mechanisms driving the adaptation of neutrophils to cancer. Yet, many questions remain: is this adaptation mediated by reprogramming mature neutrophils inside the tumoral mass, or rather by rewiring granulopoiesis in the bone marrow? Why, in some instances, are neutrophils beneficial and in others detrimental to cancer? How many different functional programs can be induced in neutrophils by tumors, and is this dependent on the type of tumor? This review summarizes what we know about these questions and discusses therapeutic strategies based on our incipient knowledge of how neutrophils adapt to cancer.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"76 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974672","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 : 2025-01-14DOI: 10.1016/j.immuni.2024.12.008
Costantino Iadecola, Josef Anrather
Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of brain-resident, meningeal, and systemic immune cells with the ischemic brain and its vasculature has emerged, and new insights into the frequent overlap between vascular and Alzheimer pathology have been provided. Here, we critically review these recent findings, place them in the context of current concepts on neurovascular pathologies and Alzheimer’s disease, and highlight their impact on recent stroke and Alzheimer therapies.
{"title":"The immunology of stroke and dementia","authors":"Costantino Iadecola, Josef Anrather","doi":"10.1016/j.immuni.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.008","url":null,"abstract":"Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of brain-resident, meningeal, and systemic immune cells with the ischemic brain and its vasculature has emerged, and new insights into the frequent overlap between vascular and Alzheimer pathology have been provided. Here, we critically review these recent findings, place them in the context of current concepts on neurovascular pathologies and Alzheimer’s disease, and highlight their impact on recent stroke and Alzheimer therapies.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"115 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974590","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 : 2025-01-06DOI: 10.1016/j.immuni.2024.12.002
Omkar Shinde, Joshua A. Boyer, Stephanie Cambier, Jordyn J. VanPortfliet, Xuewu Sui, Gaya P. Yadav, Elizabeth G. Viverette, Mario J. Borgnia, A. Phillip West, Qi Zhang, Daniel B. Stetson, Pingwei Li
Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response. However, the molecular basis of cGAMP export mediated by ABCC1 remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ABCC1 in a ligand-free state and a cGAMP-bound state. These structures reveal that ABCC1 forms a homodimer via its N-terminal transmembrane domain. The ligand-bound structure shows that cGAMP is recognized by a positively charged pocket. Mutagenesis and functional studies confirmed the roles of the ligand-binding pocket in cGAMP recognition and export. This study provides insights into the structure and function of ABCC1 as a cGAMP exporter and lays a foundation for future research targeting ABCC1 in infection and anti-cancer immunity.
{"title":"Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export","authors":"Omkar Shinde, Joshua A. Boyer, Stephanie Cambier, Jordyn J. VanPortfliet, Xuewu Sui, Gaya P. Yadav, Elizabeth G. Viverette, Mario J. Borgnia, A. Phillip West, Qi Zhang, Daniel B. Stetson, Pingwei Li","doi":"10.1016/j.immuni.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.12.002","url":null,"abstract":"Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response. However, the molecular basis of cGAMP export mediated by ABCC1 remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ABCC1 in a ligand-free state and a cGAMP-bound state. These structures reveal that ABCC1 forms a homodimer via its N-terminal transmembrane domain. The ligand-bound structure shows that cGAMP is recognized by a positively charged pocket. Mutagenesis and functional studies confirmed the roles of the ligand-binding pocket in cGAMP recognition and export. This study provides insights into the structure and function of ABCC1 as a cGAMP exporter and lays a foundation for future research targeting ABCC1 in infection and anti-cancer immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"12 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929717","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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