Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA1, like that of the phospholipase PLA2G3, the prostaglandin D2 (PGD2) synthase L-PGDS, or the PGD2 receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA. Fibroblast LPA1 then integrates multiple pathways required for MC maturation by facilitating integrin-mediated MC-fibroblast adhesion, IL-33-ST2 signaling, L-PGDS-driven PGD2 generation, and feedforward ATX-LPA1 amplification. Defective MC maturation resulting from PLA2G3 deficiency is restored by supplementation with LPA1 agonists or PLA2G3-modified EVs. Thus, the lipid-orchestrated paracrine circuit involving PLA2G3-driven lysophospholipid, eicosanoid, integrin, and cytokine signaling fine-tunes MC-fibroblast communication, ensuring MC maturation.
肥大细胞(MC)与成纤维细胞的相互作用是MC在组织微环境中成熟的必要条件,但其基本机制尚不完全清楚。通过对30个缺乏脂质相关基因的小鼠品系进行表型筛选,我们发现溶血磷脂酸(LPA)受体LPA1的缺失与磷脂酶PLA2G3、前列腺素D2(PGD2)合成酶L-PGDS或PGD2受体DP1的缺失一样,都会影响MC的成熟,从而导致过敏性休克。从机制上讲,MC 分泌的 PLA2G3 作用于细胞外囊泡 (EV),以提供溶血磷脂,溶血磷脂在成纤维细胞衍生的自旋素 (ATX) 作用下转化为 LPA。成纤维细胞 LPA1 随后通过促进整合素介导的 MC-成纤维细胞粘附、IL-33-ST2 信号传导、L-PGDS 驱动的 PGD2 生成以及 ATX-LPA1 的前馈放大,整合 MC 成熟所需的多种途径。补充 LPA1 激动剂或 PLA2G3 修饰的 EV 可恢复 PLA2G3 缺乏导致的 MC 成熟缺陷。因此,PLA2G3驱动的溶血磷脂、二十碳六烷酸、整合素和细胞因子信号的脂质协调旁分泌回路可微调MC与成纤维细胞之间的交流,从而确保MC的成熟。
{"title":"Lipid-orchestrated paracrine circuit coordinates mast cell maturation and anaphylaxis through functional interaction with fibroblasts","authors":"Yoshitaka Taketomi, Takayoshi Higashi, Kuniyuki Kano, Yoshimi Miki, Chika Mochizuki, Shota Toyoshima, Yoshimichi Okayama, Yasumasa Nishito, Susumu Nakae, Satoshi Tanaka, Suzumi M. Tokuoka, Yoshiya Oda, Shigeyuki Shichino, Satoshi Ueha, Kouji Matsushima, Noriyuki Akahoshi, Satoshi Ishii, Jerold Chun, Junken Aoki, Makoto Murakami","doi":"10.1016/j.immuni.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.012","url":null,"abstract":"<p>Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA<sub>1</sub>, like that of the phospholipase PLA2G3, the prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) synthase L-PGDS, or the PGD<sub>2</sub> receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA. Fibroblast LPA<sub>1</sub> then integrates multiple pathways required for MC maturation by facilitating integrin-mediated MC-fibroblast adhesion, IL-33-ST2 signaling, L-PGDS-driven PGD<sub>2</sub> generation, and feedforward ATX-LPA<sub>1</sub> amplification. Defective MC maturation resulting from PLA2G3 deficiency is restored by supplementation with LPA<sub>1</sub> agonists or PLA2G3-modified EVs. Thus, the lipid-orchestrated paracrine circuit involving PLA2G3-driven lysophospholipid, eicosanoid, integrin, and cytokine signaling fine-tunes MC-fibroblast communication, ensuring MC maturation.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597351","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 : 2024-07-09Epub Date: 2024-06-14DOI: 10.1016/j.immuni.2024.05.017
Barney Viengkhou, Emina Hayashida, Sarah McGlasson, Katie Emelianova, Deborah Forbes, Stewart Wiseman, Joanna Wardlaw, Rovin Verdillo, Sarosh R Irani, Darragh Duffy, Fredrik Piehl, Lipin Loo, Axel Pagenstecher, G Greg Neely, Yanick J Crow, Iain L Campbell, David P J Hunt, Markus J Hofer
Aicardi-Goutières syndrome (AGS) is an autoinflammatory disease characterized by aberrant interferon (IFN)-α production. The major cause of morbidity in AGS is brain disease, yet the primary source and target of neurotoxic IFN-α remain unclear. Here, we demonstrated that the brain was the primary source of neurotoxic IFN-α in AGS and confirmed the neurotoxicity of intracerebral IFN-α using astrocyte-driven Ifna1 misexpression in mice. Using single-cell RNA sequencing, we demonstrated that intracerebral IFN-α-activated receptor (IFNAR) signaling within cerebral endothelial cells caused a distinctive cerebral small vessel disease similar to that observed in individuals with AGS. Magnetic resonance imaging (MRI) and single-molecule ELISA revealed that central and not peripheral IFN-α was the primary determinant of microvascular disease in humans. Ablation of endothelial Ifnar1 in mice rescued microvascular disease, stopped the development of diffuse brain disease, and prolonged lifespan. These results identify the cerebral microvasculature as a primary mediator of IFN-α neurotoxicity in AGS, representing an accessible target for therapeutic intervention.
{"title":"The brain microvasculature is a primary mediator of interferon-α neurotoxicity in human cerebral interferonopathies.","authors":"Barney Viengkhou, Emina Hayashida, Sarah McGlasson, Katie Emelianova, Deborah Forbes, Stewart Wiseman, Joanna Wardlaw, Rovin Verdillo, Sarosh R Irani, Darragh Duffy, Fredrik Piehl, Lipin Loo, Axel Pagenstecher, G Greg Neely, Yanick J Crow, Iain L Campbell, David P J Hunt, Markus J Hofer","doi":"10.1016/j.immuni.2024.05.017","DOIUrl":"10.1016/j.immuni.2024.05.017","url":null,"abstract":"<p><p>Aicardi-Goutières syndrome (AGS) is an autoinflammatory disease characterized by aberrant interferon (IFN)-α production. The major cause of morbidity in AGS is brain disease, yet the primary source and target of neurotoxic IFN-α remain unclear. Here, we demonstrated that the brain was the primary source of neurotoxic IFN-α in AGS and confirmed the neurotoxicity of intracerebral IFN-α using astrocyte-driven Ifna1 misexpression in mice. Using single-cell RNA sequencing, we demonstrated that intracerebral IFN-α-activated receptor (IFNAR) signaling within cerebral endothelial cells caused a distinctive cerebral small vessel disease similar to that observed in individuals with AGS. Magnetic resonance imaging (MRI) and single-molecule ELISA revealed that central and not peripheral IFN-α was the primary determinant of microvascular disease in humans. Ablation of endothelial Ifnar1 in mice rescued microvascular disease, stopped the development of diffuse brain disease, and prolonged lifespan. These results identify the cerebral microvasculature as a primary mediator of IFN-α neurotoxicity in AGS, representing an accessible target for therapeutic intervention.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":25.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1016/j.immuni.2024.06.006
Danielle M. Clancy, Julie Andries, Savvas N. Savvides
Interleukin-1 (IL-1) family cytokines are key immunological regulators that achieve their signaling prowess after post-translational proteolytic processing. In this issue of Immunity, Dong et al. reveal the structural consequences of this process on proinflammatory IL-18, demonstrating that pro-IL-18 and mature IL-18 are structurally distinct.
{"title":"The pros and confs of IL-18 activation","authors":"Danielle M. Clancy, Julie Andries, Savvas N. Savvides","doi":"10.1016/j.immuni.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.006","url":null,"abstract":"<p>Interleukin-1 (IL-1) family cytokines are key immunological regulators that achieve their signaling prowess after post-translational proteolytic processing. In this issue of <em>Immunity</em>, Dong et al. reveal the structural consequences of this process on proinflammatory IL-18, demonstrating that pro-IL-18 and mature IL-18 are structurally distinct.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561722","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 : 2024-07-09DOI: 10.1016/j.immuni.2024.05.020
Laurent Abel, Jean-Laurent Casanova
Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.
无论微生物的毒力(即全球感染-死亡比率)如何,年龄通常会影响未接种疫苗的人类因感染而死亡的流行率。目前已发现四种死亡模式:流行性感染常见的 U 型和 L 型曲线,以及大流行性感染特有的 W 型和 J 型曲线。我们认为,这些模式是由不同的人类基因和免疫决定因素造成的。在这一模式中,(1) 影响原发性感染免疫力的单基因型在生命早期优先显现,相关基因型或其表型(包括自身抗体)在生命晚期显现,(2) 对原发性感染或交叉反应感染的适应性获得性免疫的发生和持续,这两者之间的相互作用形成了人类死于感染的年龄依赖模式。
{"title":"Human determinants of age-dependent patterns of death from infection","authors":"Laurent Abel, Jean-Laurent Casanova","doi":"10.1016/j.immuni.2024.05.020","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.05.020","url":null,"abstract":"<p>Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561767","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 : 2024-07-09Epub Date: 2024-05-21DOI: 10.1016/j.immuni.2024.04.027
Joseph Jorssen, Glenn Van Hulst, Kiréna Mollers, Julien Pujol, Georgios Petrellis, Antonio P Baptista, Sjoerd Schetters, Frédéric Baron, Jo Caers, Bart N Lambrecht, Benjamin G Dewals, Fabrice Bureau, Christophe J Desmet
The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.
{"title":"Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification.","authors":"Joseph Jorssen, Glenn Van Hulst, Kiréna Mollers, Julien Pujol, Georgios Petrellis, Antonio P Baptista, Sjoerd Schetters, Frédéric Baron, Jo Caers, Bart N Lambrecht, Benjamin G Dewals, Fabrice Bureau, Christophe J Desmet","doi":"10.1016/j.immuni.2024.04.027","DOIUrl":"10.1016/j.immuni.2024.04.027","url":null,"abstract":"<p><p>The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":25.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081270","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 : 2024-07-09DOI: 10.1016/j.immuni.2024.06.004
Eliana R. Solis, Julie M. Jameson
Skin inflammation is potentiated by coordinated epithelial and immune cell metabolism. In this issue of Immunity, Subudhi and Konieczny et al. delineate how HIF1α regulates epithelial cell glycolysis during psoriasis. In turn, lactate is a byproduct that augments type 17 γδ T cell responses to sustain inflammatory skin disease.
{"title":"Skin deep: Epithelial cell metabolism and chronic skin inflammation","authors":"Eliana R. Solis, Julie M. Jameson","doi":"10.1016/j.immuni.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.004","url":null,"abstract":"<p>Skin inflammation is potentiated by coordinated epithelial and immune cell metabolism. In this issue of <em>Immunity</em>, Subudhi and Konieczny et al. delineate how HIF1α regulates epithelial cell glycolysis during psoriasis. In turn, lactate is a byproduct that augments type 17 γδ T cell responses to sustain inflammatory skin disease.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561724","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 : 2024-07-09DOI: 10.1016/j.immuni.2024.06.002
Nicholas W. Hubbard, Andrew Oberst
RIPK1 is known as a driver of cell death and inflammation. In this issue of Immunity, Imai et al. and Mannion et al. find that these same processes are also induced by RIPK1 inactivation and highlight the therapeutic potential of RIPK1 elimination.
{"title":"RIPK1: Inflamed if you do, inflamed if you don’t","authors":"Nicholas W. Hubbard, Andrew Oberst","doi":"10.1016/j.immuni.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.002","url":null,"abstract":"<p>RIPK1 is known as a driver of cell death and inflammation. In this issue of <em>Immunity</em>, Imai et al. and Mannion et al. find that these same processes are also induced by RIPK1 inactivation and highlight the therapeutic potential of RIPK1 elimination.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561745","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 : 2024-07-09DOI: 10.1016/j.immuni.2024.06.008
Jadie Y. Moon, Katherine A. Gallagher
Autoreactive lymphocytes that infiltrate the pancreatic islet environment and target β cells are primary drivers of type 1 diabetes. In this issue of Immunity, Srivastava et al.1 examine the role of the islet microenvironment in autoimmunity and find that the scavenging receptor CXCL16 on islet-resident macrophages uptakes oxidized low-density lipoproteins and promotes the differentiation and survival of infiltrating pathogenic CD8+ T cells.
浸润胰岛环境并以β细胞为靶细胞的自身反应性淋巴细胞是1型糖尿病的主要诱因。在本期《免疫》杂志上,Srivastava 等人1 研究了胰岛微环境在自身免疫中的作用,发现胰岛驻留巨噬细胞上的清除受体 CXCL16 能吸收氧化的低密度脂蛋白,并促进浸润的致病性 CD8+ T 细胞的分化和存活。
{"title":"Scavengers in islets fuel diabetic autoimmunity","authors":"Jadie Y. Moon, Katherine A. Gallagher","doi":"10.1016/j.immuni.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.008","url":null,"abstract":"<p>Autoreactive lymphocytes that infiltrate the pancreatic islet environment and target β cells are primary drivers of type 1 diabetes. In this issue of <em>Immunity</em>, Srivastava et al.<span><sup>1</sup></span> examine the role of the islet microenvironment in autoimmunity and find that the scavenging receptor CXCL16 on islet-resident macrophages uptakes oxidized low-density lipoproteins and promotes the differentiation and survival of infiltrating pathogenic CD8<sup>+</sup> T cells.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561723","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 : 2024-07-09DOI: 10.1016/j.immuni.2024.06.007
Guilhem Pupier, Catherine Sautès-Fridman
The association of tertiary lymphoid structures (TLSs) with survival and immunotherapy response brought B cells to center stage. In a pan-cancer B cells atlas in Science, Ma et al. show that germinal center reaction generating anti-tumor antibody-secreting cells (ASCs) from B memory cells in mature TLSs co-exist in tumors with extra-follicular reaction generating auto-reactive ASCs from memory B cells in immature TLSs.
三级淋巴结构(TLSs)与生存和免疫治疗反应的关系使 B 细胞成为研究的中心。Ma 等人在《科学》(Science)杂志上发表的泛癌症 B 细胞图谱中显示,成熟三级淋巴结构中由 B 记忆细胞产生抗肿瘤抗体分泌细胞(ASCs)的生殖中心反应与未成熟三级淋巴结构中由记忆 B 细胞产生自身反应 ASCs 的滤泡外反应同时存在于肿瘤中。
{"title":"B cells! Don’t go the wrong way in this tumor","authors":"Guilhem Pupier, Catherine Sautès-Fridman","doi":"10.1016/j.immuni.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.06.007","url":null,"abstract":"<p>The association of tertiary lymphoid structures (TLSs) with survival and immunotherapy response brought B cells to center stage. In a pan-cancer B cells atlas in <em>Science</em>, Ma et al. show that germinal center reaction generating anti-tumor antibody-secreting cells (ASCs) from B memory cells in mature TLSs co-exist in tumors with extra-follicular reaction generating auto-reactive ASCs from memory B cells in immature TLSs.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561725","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}