Science Immunology最新文献

{"title":"When a double negative is not a positive: Autoantibodies against IL-10 in patients with inflammatory bowel disease","authors":"Colleen M. Noviello","doi":"10.1126/sciimmunol.ads7642","DOIUrl":"10.1126/sciimmunol.ads7642","url":null,"abstract":"<div >IL-10 autoantibodies are detected in two patients with severe inflammatory bowel disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143378","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}

{"title":"The promise of priming precursors: Advances in inducing CD4 binding site–directed HIV broadly neutralizing antibodies","authors":"Rama Rao Amara","doi":"10.1126/sciimmunol.adq8862","DOIUrl":"10.1126/sciimmunol.adq8862","url":null,"abstract":"<div >HIV envelope immunogen designed to activate germline B cell precursors of CD4 binding site–specific neutralizing antibodies shows promise in monkeys.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100525","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}

{"title":"Immunization with germ line–targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques","authors":"Ashley N. Nelson,&nbsp;Xiaoying Shen,&nbsp;Sravani Vekatayogi,&nbsp;Shiyu Zhang,&nbsp;Gabriel Ozorowski,&nbsp;Maria Dennis,&nbsp;Leigh M. Sewall,&nbsp;Emma Milligan,&nbsp;Dominique Davis,&nbsp;Kaitlyn A. Cross,&nbsp;Yue Chen,&nbsp;Jelle van Schooten,&nbsp;Joshua Eudailey,&nbsp;John Isaac,&nbsp;Saad Memon,&nbsp;Carolyn Weinbaum,&nbsp;Hongmei Gao,&nbsp;Sherry Stanfield-Oakley,&nbsp;Alliyah Byrd,&nbsp;Suni Chutkan,&nbsp;Stella Berendam,&nbsp;Kenneth Cronin,&nbsp;Anila Yasmeen,&nbsp;S. Munir Alam,&nbsp;Celia C. LaBranche,&nbsp;Kenneth Rogers,&nbsp;Lisa Shirreff,&nbsp;Albert Cupo,&nbsp;Ronald Derking,&nbsp;Francois Villinger,&nbsp;Per Johan Klasse,&nbsp;Guido Ferrari,&nbsp;Wilton B. Williams,&nbsp;Michael G. Hudgens,&nbsp;Andrew B. Ward,&nbsp;David C. Montefiori,&nbsp;Koen K. A. Van Rompay,&nbsp;Kevin Wiehe,&nbsp;John P. Moore,&nbsp;Rogier W. Sanders,&nbsp;Kristina De Paris,&nbsp;Sallie R. Permar","doi":"10.1126/sciimmunol.adm7097","DOIUrl":"10.1126/sciimmunol.adm7097","url":null,"abstract":"<div >Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage–designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41—named “SOS”—and an isoleucine-to-proline point mutation—named “IP”—at residue 559) to induce precursor CD4 binding site (CD4bs)–targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line–targeting BG505 SOSIP GT1.1 (<i>n</i> = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants (<i>n</i> = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage–designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100585","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}

{"title":"Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site","authors":"Tom G. Caniels,&nbsp;Max Medina-Ramìrez,&nbsp;Shiyu Zhang,&nbsp;Sven Kratochvil,&nbsp;Yuejiao Xian,&nbsp;Ja-Hyun Koo,&nbsp;Ronald Derking,&nbsp;Jakob Samsel,&nbsp;Jelle van Schooten,&nbsp;Simone Pecetta,&nbsp;Edward Lamperti,&nbsp;Meng Yuan,&nbsp;María Ríos Carrasco,&nbsp;Iván del Moral Sánchez,&nbsp;Joel D. Allen,&nbsp;Joey H. Bouhuijs,&nbsp;Anila Yasmeen,&nbsp;Thomas J. Ketas,&nbsp;Jonne L. Snitselaar,&nbsp;Tom P. L. Bijl,&nbsp;Isabel Cuella Martin,&nbsp;Jonathan L. Torres,&nbsp;Albert Cupo,&nbsp;Lisa Shirreff,&nbsp;Kenneth Rogers,&nbsp;Rosemarie D. Mason,&nbsp;Mario Roederer,&nbsp;Kelli M. Greene,&nbsp;Hongmei Gao,&nbsp;Catarina Mendes Silva,&nbsp;Isabel J. L. Baken,&nbsp;Ming Tian,&nbsp;Frederick W. Alt,&nbsp;Bali Pulendran,&nbsp;Michael S. Seaman,&nbsp;Max Crispin,&nbsp;Marit J. van Gils,&nbsp;David C. Montefiori,&nbsp;Adrian B. McDermott,&nbsp;François J. Villinger,&nbsp;Richard A. Koup,&nbsp;John P. Moore,&nbsp;Per Johan Klasse,&nbsp;Gabriel Ozorowski,&nbsp;Facundo D. Batista,&nbsp;Ian A. Wilson,&nbsp;Andrew B. Ward,&nbsp;Rogier W. Sanders","doi":"10.1126/sciimmunol.adk9550","DOIUrl":"10.1126/sciimmunol.adk9550","url":null,"abstract":"<div >Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100523","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}

{"title":"PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells","authors":"Alessio Bevilacqua,&nbsp;Fabien Franco,&nbsp;Ya-Ting Lu,&nbsp;Nabil Rahiman,&nbsp;Kung-Chi Kao,&nbsp;Yu-Ming Chuang,&nbsp;Yanan Zhu,&nbsp;Werner Held,&nbsp;Xin Xie,&nbsp;Kristin C. Gunsalus,&nbsp;Zhengtao Xiao,&nbsp;Shih-Yu Chen,&nbsp;Ping-Chih Ho","doi":"10.1126/sciimmunol.adn2717","DOIUrl":"10.1126/sciimmunol.adn2717","url":null,"abstract":"<div >The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8⁺ T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044165","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}

{"title":"Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved","authors":"Merve Aksöz,&nbsp;Grigore-Aristide Gafencu,&nbsp;Bilyana Stoilova,&nbsp;Mario Buono,&nbsp;Ying Zhang,&nbsp;Sven Turkalj,&nbsp;Yiran Meng,&nbsp;Niels Asger Jakobsen,&nbsp;Marlen Metzner,&nbsp;Sally-Ann Clark,&nbsp;Ryan Beveridge,&nbsp;Supat Thongjuea,&nbsp;Paresh Vyas,&nbsp;Claus Nerlov","doi":"10.1126/sciimmunol.adk3469","DOIUrl":"10.1126/sciimmunol.adk3469","url":null,"abstract":"<div >Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044163","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}

{"title":"Mast cell–derived BH4 and serotonin are critical mediators of postoperative pain","authors":"Philipp Starkl,&nbsp;Gustav Jonsson,&nbsp;Tyler Artner,&nbsp;Bruna Lenfers Turnes,&nbsp;Laura-Marie Gail,&nbsp;Tiago Oliveira,&nbsp;Aakanksha Jain,&nbsp;Nadine Serhan,&nbsp;Karel Stejskal,&nbsp;Karin Lakovits,&nbsp;Anastasiya Hladik,&nbsp;Meilin An,&nbsp;Keith M. Channon,&nbsp;Hail Kim,&nbsp;Thomas Köcher,&nbsp;Wolfgang Weninger,&nbsp;Georg Stary,&nbsp;Sylvia Knapp,&nbsp;Victoria Klang,&nbsp;Nicolas Gaudenzio,&nbsp;Clifford J. Woolf,&nbsp;Shweta Tikoo,&nbsp;Rohit Jain,&nbsp;Josef M. Penninger,&nbsp;Shane J. F. Cronin","doi":"10.1126/sciimmunol.adh0545","DOIUrl":"10.1126/sciimmunol.adh0545","url":null,"abstract":"<div >Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of <i>Gch1</i>, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell–specific <i>Gch1</i> or <i>Tph1</i> showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P–driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044164","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}

{"title":"Context-dependent role of group 3 innate lymphoid cells in mucosal protection","authors":"Leandro P. Araujo,&nbsp;Madeline Edwards,&nbsp;Koichiro Irie,&nbsp;Yiming Huang,&nbsp;Yoshinaga Kawano,&nbsp;Alexander Tran,&nbsp;Simona De Michele,&nbsp;Govind Bhagat,&nbsp;Harris H. Wang,&nbsp;Ivaylo I. Ivanov","doi":"10.1126/sciimmunol.ade7530","DOIUrl":"10.1126/sciimmunol.ade7530","url":null,"abstract":"<div >How group 3 innate lymphoid cells (ILC3s) regulate mucosal protection in the presence of T cells remains poorly understood. Here, we examined ILC3 function in intestinal immunity using ILC3-deficient mice that maintain endogenous T cells, T helper 17 (T_H17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T_H17 and T_H22 cell responses to commensal and pathogenic bacteria, and absence of ILC3s did not affect IL-22 production by CD4 T cells before or during infection. However, despite the presence of IL-22–producing T cells, ILC3s and ILC3-derived IL-22 were required for maintaining homeostatic functions of the intestinal epithelium. T cell–sufficient, ILC3-deficient mice were capable of pathogen clearance and survived infection with a low dose of <i>Citrobacter rodentium</i>. However, ILC3s promoted pathogen tolerance at early time points of infection by activating tissue-protective immune pathways. Consequently, ILC3s were indispensable for survival after high-dose infection. Our results demonstrate a context-dependent role for ILC3s in immune-sufficient animals and provide a blueprint for uncoupling of ILC3 and T_H17 cell functions.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992387","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}

{"title":"Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities","authors":"Andrew R. Patterson,&nbsp;Gabriel A. Needle,&nbsp;Ayaka Sugiura,&nbsp;Erin Q. Jennings,&nbsp;Channing Chi,&nbsp;KayLee K. Steiner,&nbsp;Emilie L. Fisher,&nbsp;Gabriella L. Robertson,&nbsp;Caroline Bodnya,&nbsp;Janet G. Markle,&nbsp;Ryan D. Sheldon,&nbsp;Russell G. Jones,&nbsp;Vivian Gama,&nbsp;Jeffrey C. Rathmell","doi":"10.1126/sciimmunol.adh0368","DOIUrl":"10.1126/sciimmunol.adh0368","url":null,"abstract":"<div >Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover. Analysis of IEMs showed that N-linked glycosylation and the hexosamine pathway enzyme <i>Gfpt1</i> are critical for T cell expansion and function. Further, T helper (T_H1) cells synthesized uridine diphosphate <i>N</i>-acetylglucosamine more rapidly and were more impaired by <i>Gfpt1</i> deficiency than T_H17 cells. Screening IEI genes found that <i>Bcl11b</i> promotes the CD4 T cell mitochondrial activity and <i>Mcl1</i> expression necessary to prevent metabolic stress. Thus, a high degree of functional overlap exists between IEM and IEI genes, and immunometabolic mechanisms may underlie a previously underappreciated intersection of these disorders.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992052","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}

{"title":"Erratum for the Research Article “SARS-CoV-2 inflammation durably imprints memory CD4 T cells” by S. L. Gray-Gaillard et al.","authors":"","doi":"10.1126/sciimmunol.adr9665","DOIUrl":"10.1126/sciimmunol.adr9665","url":null,"abstract":"","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 98","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992388","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}