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The Sixth Sense: Self-nucleic acid sensing in the brain. 第六感大脑中的自核酸感应
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-05-03 DOI: 10.1016/bs.ai.2024.03.001
Tyler J Dorrity, Heegwon Shin, Jake A Gertie, Hachung Chung
{"title":"The Sixth Sense: Self-nucleic acid sensing in the brain.","authors":"Tyler J Dorrity, Heegwon Shin, Jake A Gertie, Hachung Chung","doi":"10.1016/bs.ai.2024.03.001","DOIUrl":"10.1016/bs.ai.2024.03.001","url":null,"abstract":"<p><p>Our innate immune system uses pattern recognition receptors (PRRs) as a first line of defense to detect microbial ligands and initiate an immune response. Viral nucleic acids are key ligands for the activation of many PRRs and the induction of downstream inflammatory and antiviral effects. Initially it was thought that endogenous (self) nucleic acids rarely activated these PRRs, however emerging evidence indicates that endogenous nucleic acids are able to activate host PRRs in homeostasis and disease. In fact, many regulatory mechanisms are in place to finely control and regulate sensing of self-nucleic acids by PRRs. Sensing of self-nucleic acids is particularly important in the brain, as perturbations to nucleic acid sensing commonly leads to neuropathology. This review will highlight the role of nucleic acid sensors in the brain, both in disease and homeostasis. We also indicate the source of endogenous stimulatory nucleic acids where known and summarize future directions for the study of this growing field.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"161 ","pages":"53-83"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The molecular mechanism of dsDNA sensing through the cGAS-STING pathway. 通过 cGAS-STING 通路感知 dsDNA 的分子机制。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-03-02 DOI: 10.1016/bs.ai.2024.02.003
Omkar Shinde, Pingwei Li
{"title":"The molecular mechanism of dsDNA sensing through the cGAS-STING pathway.","authors":"Omkar Shinde, Pingwei Li","doi":"10.1016/bs.ai.2024.02.003","DOIUrl":"10.1016/bs.ai.2024.02.003","url":null,"abstract":"<p><p>Double stranded DNA (dsDNA) in the cytoplasm triggers the cGAS-STING innate immune pathway to defend against pathogenic infections, tissue damage and malignant cells. Extensive structural and functional studies over the last couple of years have enabled the molecular understanding of dsDNA induced activation of the cGAS-STING signaling pathway. This review highlights recent advances in the structural characterization of key molecules in the cGAS-STING signaling axis by focusing on the mechanism of cGAS activation by dsDNA, the regulation of cGAS activity, the mechanism of STING activation by cGAMP, the molecular basis of TBK1 recruitment and activation by STING, the structural basis of IRF3 recruitment by STING, and the mechanism of IRF3 activation upon phosphorylation by TBK1. These comprehensive structural studies provide a detailed picture of the mechanism of the cGAS-STING signaling pathway, establishing a molecular framework for the development of novel therapeutic strategies targeting this pathway.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"162 ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Post-transcriptional (re)programming of B lymphocyte development: From bench to bedside? B 淋巴细胞发育的转录后（重）编程：从工作台到床边？
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-03-21 DOI: 10.1016/bs.ai.2024.03.003
Alia M Welsh, Stefan A Muljo
{"title":"Post-transcriptional (re)programming of B lymphocyte development: From bench to bedside?","authors":"Alia M Welsh, Stefan A Muljo","doi":"10.1016/bs.ai.2024.03.003","DOIUrl":"10.1016/bs.ai.2024.03.003","url":null,"abstract":"<p><p>Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here, we will focus on the post-transcriptional differences between fetal liver (FL) and adult bone marrow (ABM) HSCs. It remains unclear how or why exactly FL HSCs transition to ABM HSCs, but we aim to leverage their differences to revive an old idea: in utero HSC transplantation. Unexpectedly, the expression of certain RNA-binding proteins (RBPs) play an important role in HSC specification, and can be employed to convert or reprogram adult HSCs back to a fetal-like state. Among other features, FL HSCs have a broad differentiation capacity that includes the ability to regenerate both conventional B and T cells, as well as innate-like or unconventional lymphocytes such as B-1a and marginal zone B (MzB) cells. This chapter will focus on RNA binding proteins, namely LIN28B and IGF2BP3, that are expressed during fetal life and how they promote B-1a cell development. Furthermore, this chapter considers a potential clinical application of synthetic co-expression of LIN28B and IGF2BP3 in HSCs.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"161 ","pages":"85-108"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The multifaceted roles of TCF1 in innate and adaptive lymphocytes. TCF1 在先天性和适应性淋巴细胞中的多重作用。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-10-22 DOI: 10.1016/bs.ai.2024.10.001
Matthew McCullen, Eugene Oltz
{"title":"The multifaceted roles of TCF1 in innate and adaptive lymphocytes.","authors":"Matthew McCullen, Eugene Oltz","doi":"10.1016/bs.ai.2024.10.001","DOIUrl":"https://doi.org/10.1016/bs.ai.2024.10.001","url":null,"abstract":"<p><p>The immune system requires a complex network of specialized cell types to defend against a range of threats. The specific roles and destinies of these cell types are enforced by a constellation of gene regulatory programs, which are orchestrated through lineage-specifying transcription factors. T Cell Factor 1 (TCF1) is a central transcription factor in many of these programs, guiding the development and functionality of both adaptive and innate lymphoid cells. This review highlights recent insights into the function of TCF1 in a variety of lymphoid cell subsets and its potential for translational applications in immune disorders and cancer.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"164 ","pages":"39-71"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alternative DNA structures in hematopoiesis and adaptive immunity. 造血和适应性免疫中的另类 DNA 结构。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-03-19 DOI: 10.1016/bs.ai.2024.03.002
Heather Kligfeld, Isabella Han, Ajay Abraham, Vipul Shukla
{"title":"Alternative DNA structures in hematopoiesis and adaptive immunity.","authors":"Heather Kligfeld, Isabella Han, Ajay Abraham, Vipul Shukla","doi":"10.1016/bs.ai.2024.03.002","DOIUrl":"10.1016/bs.ai.2024.03.002","url":null,"abstract":"<p><p>Besides the canonical B-form, DNA also adopts alternative non-B form conformations which are highly conserved in all domains of life. While extensive research over decades has centered on the genomic functions of B-form DNA, understanding how non-B-form conformations influence functional genomic states remains a fundamental and open question. Recent studies have ascribed alternative DNA conformations such as G-quadruplexes and R-loops as important functional features in eukaryotic genomes. This review delves into the biological importance of alternative DNA structures, with a specific focus on hematopoiesis and adaptive immunity. We discuss the emerging roles of G-quadruplex and R-loop structures, the two most well-studied alternative DNA conformations, in the hematopoietic compartment and present evidence for their functional roles in normal cellular physiology and associated pathologies.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"161 ","pages":"109-126"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The regulation of the apoptotic pore-An immunological tightrope walk. 凋亡孔的调节--走在免疫学的钢丝上。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-05-06 DOI: 10.1016/bs.ai.2024.02.004
Andreas Jenner, Ana J Garcia-Saez
{"title":"The regulation of the apoptotic pore-An immunological tightrope walk.","authors":"Andreas Jenner, Ana J Garcia-Saez","doi":"10.1016/bs.ai.2024.02.004","DOIUrl":"10.1016/bs.ai.2024.02.004","url":null,"abstract":"<p><p>Apoptotic pore formation in mitochondria is the pivotal point for cell death during mitochondrial apoptosis. It is regulated by BCL-2 family proteins in response to various cellular stress triggers and mediates mitochondrial outer membrane permeabilization (MOMP). This allows the release of mitochondrial contents into the cytosol, which triggers rapid cell death and clearance through the activation of caspases. However, under conditions of low caspase activity, the mitochondrial contents released into the cytosol through apoptotic pores serve as inflammatory signals and activate various inflammatory responses. In this chapter, we discuss how the formation of the apoptotic pore is regulated by BCL-2 proteins as well as other cellular or mitochondrial proteins and membrane lipids. Moreover, we highlight the importance of sublethal MOMP in the regulation of mitochondrial-activated inflammation and discuss its physiological consequences in the context of pathogen infection and disease and how it can potentially be exploited therapeutically, for example to improve cancer treatment.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"162 ","pages":"59-108"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of autophagy in RIP1 mediated cell death and intestinal inflammation. 自噬在 RIP1 介导的细胞死亡和肠道炎症中的作用。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-08-31 DOI: 10.1016/bs.ai.2024.07.003
Yujung Michelle Lee, Domagoj Vucic
{"title":"The role of autophagy in RIP1 mediated cell death and intestinal inflammation.","authors":"Yujung Michelle Lee, Domagoj Vucic","doi":"10.1016/bs.ai.2024.07.003","DOIUrl":"https://doi.org/10.1016/bs.ai.2024.07.003","url":null,"abstract":"<p><p>Autophagy, a highly conserved catabolic process that targets various types of cellular cargoes to lysosomal degradation, is one of the most important biological mechanisms critical for cellular homeostasis. Components of these cellular cargoes can range from individual proteins to invading pathogens, and degrading these materials is important for maintaining organismal health and survival. The process of autophagy is carried out by complex molecular mechanisms, and a growing body of evidence indicates that these mechanisms intersect with those involved in the cell death pathways. In this review, we examine several emerging studies elucidating the role of autophagy in RIP1-mediated cell death signaling, with particular emphasis on impaired autophagy caused by ATG16L1 deficiency. We also discuss how autophagy in RIP1-mediated cell death affects intestinal homeostasis in preclinical models, and the implications of the intersection between RIP1 and autophagy for understanding the intestinal pathologies associated with inflammatory bowel disease (IBD). Finally, we highlight the potential benefits of therapeutic targeting of RIP1 and autophagy proteins, while also proposing areas of research that will likely elucidate new links between autophagy and cell death signaling.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"163 ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anatomy of a superenhancer. 超级增能器解剖图
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-08-31 DOI: 10.1016/bs.ai.2024.08.001
Sunkyung Kim, Tian-Tian Liu, Feiya Ou, Theresa L Murphy, Kenneth M Murphy
{"title":"Anatomy of a superenhancer.","authors":"Sunkyung Kim, Tian-Tian Liu, Feiya Ou, Theresa L Murphy, Kenneth M Murphy","doi":"10.1016/bs.ai.2024.08.001","DOIUrl":"https://doi.org/10.1016/bs.ai.2024.08.001","url":null,"abstract":"<p><p>Interferon regulatory factor-8 (IRF8) is the lineage determining transcription factor for the type one classical dendritic cell (cDC1) subset, a terminal selector for plasmacytoid dendritic cells and important for the function of monocytes. Studies of Irf8 gene regulation have identified several enhancers controlling its activity during development of progenitors in the bone marrow that precisely regulate expression at distinct developmental stages. Each enhancer responds to distinct transcription factors that are expressed at each stage. IRF8 is first expressed in early progenitors that form the monocyte dendritic cell progenitor (MDP) in response to induction of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) acting at the Irf8 +56 kb enhancer. IRF8 levels increase further as the MDP transits into the common dendritic cell progenitor (CDP) in response to E protein activity at the Irf8 +41 kb enhancer. Upon Nfil3-induction in CDPs leading to specification of the cDC1 progenitor, abrupt induction of BATF3 forms the JUN/BATF3/IRF8 heterotrimer that activates the Irf8 +32 kb enhancer that sustains Irf8 autoactivation throughout the cDC1 lifetime. Deletions of each of these enhancers has revealed their stage dependent activation. Surprisingly, studies of compound heterozygotes for each combination of enhancer deletions revealed that activation of each subsequent enhancer requires the successful activation of the previous enhancer in strictly cis-dependent mechanism. Successful progression of enhancer activation is finely tuned to alter the functional accessibility of subsequent enhancers to factors active in the next stage of development. The molecular basis for these phenomenon is still obscure but could have implications for genomic regulation in a broader developmental context.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"163 ","pages":"51-96"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Germinal center versus extrafollicular responses in systemic autoimmunity: Who turns the blade on self? 系统性自身免疫中的发芽中心与滤泡外反应：谁在向自己开刀？
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-03-06 DOI: 10.1016/bs.ai.2024.02.002
Yuke He, Carola G Vinuesa
{"title":"Germinal center versus extrafollicular responses in systemic autoimmunity: Who turns the blade on self?","authors":"Yuke He, Carola G Vinuesa","doi":"10.1016/bs.ai.2024.02.002","DOIUrl":"10.1016/bs.ai.2024.02.002","url":null,"abstract":"<p><p>Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinity autoantibodies, but their role in autoimmunity is becoming increasingly controversial, particularly in the context of systemic autoimmune diseases like lupus. On the one hand, there is good evidence that some pathogenic lupus antibodies have acquired somatic mutations that increase affinity for self-antigens. On the other hand, recent studies that have genetically prevented GC formation, suggest that GCs are dispensable for systemic autoimmunity, pointing instead to pathogenic extrafollicular (EF) B-cell responses. Furthermore, several lines of evidence suggest germinal centers may in fact be somewhat protective in the context of autoimmunity. Here we review how some of the conflicting evidence arose, and current views on the role of GCs in autoimmunity, outlining mechanisms by which GC may eliminate self-reactivity. We also discuss recent advances in understanding extrafollicular B cell subsets that participate in autoimmunity.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"162 ","pages":"109-133"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IL-17 family cytokines in inflammatory or autoimmune skin diseases. 炎症性或自身免疫性皮肤病中的 IL-17 家族细胞因子。
3区 医学
Advances in Immunology Pub Date : 2024-01-01 Epub Date: 2024-08-13 DOI: 10.1016/bs.ai.2024.07.002
Baida Kong, Yuping Lai
{"title":"IL-17 family cytokines in inflammatory or autoimmune skin diseases.","authors":"Baida Kong, Yuping Lai","doi":"10.1016/bs.ai.2024.07.002","DOIUrl":"https://doi.org/10.1016/bs.ai.2024.07.002","url":null,"abstract":"<p><p>As potent pro-inflammatory mediators, IL-17 family cytokines play crucial roles in the pathogenesis of various inflammatory and autoimmune skin disorders. Although substantial progress has been achieved in understanding the pivotal role of IL-17A signaling in psoriasis, leading to the development of highly effective biologics, the functions of other IL-17 family members in inflammatory or autoimmune skin diseases remain less explored. In this review, we provide a comprehensive overview of IL-17 family cytokines and their receptors, with a particular focus on the recent advancements in identifying cellular sources, receptors and signaling pathways regulated by these cytokines. At the end, we discuss how the aberrant functions of IL-17 family cytokines contribute to the pathogenesis of diverse inflammatory or autoimmune skin diseases.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"163 ","pages":"21-49"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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