Jianglin Zhang, Guoxun Wang, Junjie Ma, Yiran Duan, Samskrathi A. Sharma, Sarah Oladejo, Xianda Ma, Giselle Arellano, Robert C. Orchard, Tiffany A. Reese, Zheng Kuang
{"title":"HDAC3 integrates TGF-β and microbial cues to program tuft cell biogenesis and diurnal rhythms in mucosal immune surveillance","authors":"Jianglin Zhang, Guoxun Wang, Junjie Ma, Yiran Duan, Samskrathi A. Sharma, Sarah Oladejo, Xianda Ma, Giselle Arellano, Robert C. Orchard, Tiffany A. Reese, Zheng Kuang","doi":"10.1126/sciimmunol.adk7387","DOIUrl":"10.1126/sciimmunol.adk7387","url":null,"abstract":"<div >The intestinal mucosal surface is directly exposed to daily fluctuations in food and microbes driven by 24-hour light and feeding cycles. Intestinal epithelial tuft cells are key sentinels that surveil the gut luminal environment, but how these cells are diurnally programmed remains unknown. Here, we show that histone deacetylase 3 (HDAC3) controls tuft cell specification and the diurnal rhythm of its biogenesis, which is regulated by the gut microbiota and feeding schedule. Disruption of epithelial HDAC3 decreases tuft cell numbers, impairing antihelminth immunity and norovirus infection. Mechanistically, HDAC3 functions noncanonically to activate transforming growth factor–β (TGF-β) signaling, which promotes rhythmic expression of <i>Pou2f3</i>, a lineage-defining transcription factor of tuft cells. Our findings reveal an environmental-epigenetic link that controls the diurnal differentiation of tuft cells and promotes rhythmic mucosal surveillance and immune responses in anticipation of exogenous challenges.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325678","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}
Vladyslav Kavaka, Luisa Mutschler, Clara de la Rosa del Val, Klara Eglseer, Ana M. Gómez Martínez, Andrea Flierl-Hecht, Birgit Ertl-Wagner, Daniel Keeser, Martin Mortazavi, Klaus Seelos, Hanna Zimmermann, Jürgen Haas, Brigitte Wildemann, Tania Kümpfel, Klaus Dornmair, Thomas Korn, Reinhard Hohlfeld, Martin Kerschensteiner, Lisa Ann Gerdes, Eduardo Beltrán
{"title":"Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis","authors":"Vladyslav Kavaka, Luisa Mutschler, Clara de la Rosa del Val, Klara Eglseer, Ana M. Gómez Martínez, Andrea Flierl-Hecht, Birgit Ertl-Wagner, Daniel Keeser, Martin Mortazavi, Klaus Seelos, Hanna Zimmermann, Jürgen Haas, Brigitte Wildemann, Tania Kümpfel, Klaus Dornmair, Thomas Korn, Reinhard Hohlfeld, Martin Kerschensteiner, Lisa Ann Gerdes, Eduardo Beltrán","doi":"10.1126/sciimmunol.adj8094","DOIUrl":"10.1126/sciimmunol.adj8094","url":null,"abstract":"<div >Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8<sup>+</sup> T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8<sup>+</sup> T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8<sup>+</sup> T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8<sup>+</sup> T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj8094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325683","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}
Sachin H. Bhagchandani, Leerang Yang, Jonathan H. Lam, Laura Maiorino, Elana Ben-Akiva, Kristen A. Rodrigues, Anna Romanov, Heikyung Suh, Aereas Aung, Shengwei Wu, Anika Wadhera, Arup K. Chakraborty, Darrell J. Irvine
{"title":"Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response","authors":"Sachin H. Bhagchandani, Leerang Yang, Jonathan H. Lam, Laura Maiorino, Elana Ben-Akiva, Kristen A. Rodrigues, Anna Romanov, Heikyung Suh, Aereas Aung, Shengwei Wu, Anika Wadhera, Arup K. Chakraborty, Darrell J. Irvine","doi":"10.1126/sciimmunol.adl3755","DOIUrl":"10.1126/sciimmunol.adl3755","url":null,"abstract":"<div >Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T<sub>FH</sub> responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of T<sub>FH</sub> priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adl3755","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275197","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}
Darren R. Heintzman, Rachael C. Sinard, Emilie L. Fisher, Xiang Ye, Andrew R. Patterson, Joel H. Elasy, Kelsey Voss, Channing Chi, Ayaka Sugiura, Gabriel J. Rodriguez-Garcia, Nowrin U. Chowdhury, Emily N. Arner, Evan S. Krystoviak, Frank M. Mason, Yasmine T. Toudji, KayLee K. Steiner, Wasay Khan, Lana M. Olson, Angela L. Jones, Hanna S. Hong, Lindsay Bass, Katherine L. Beier, Wentao Deng, Costas A. Lyssiotis, Dawn C. Newcomb, Alexander G. Bick, W. Kimryn Rathmell, John T. Wilson, Jeffrey C. Rathmell
{"title":"Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation","authors":"Darren R. Heintzman, Rachael C. Sinard, Emilie L. Fisher, Xiang Ye, Andrew R. Patterson, Joel H. Elasy, Kelsey Voss, Channing Chi, Ayaka Sugiura, Gabriel J. Rodriguez-Garcia, Nowrin U. Chowdhury, Emily N. Arner, Evan S. Krystoviak, Frank M. Mason, Yasmine T. Toudji, KayLee K. Steiner, Wasay Khan, Lana M. Olson, Angela L. Jones, Hanna S. Hong, Lindsay Bass, Katherine L. Beier, Wentao Deng, Costas A. Lyssiotis, Dawn C. Newcomb, Alexander G. Bick, W. Kimryn Rathmell, John T. Wilson, Jeffrey C. Rathmell","doi":"10.1126/sciimmunol.adp3475","DOIUrl":"10.1126/sciimmunol.adp3475","url":null,"abstract":"<div >Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T<sub>H</sub>1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways. Although many T<sub>H</sub>1 cells subjected to such temperatures died, surviving T<sub>H</sub>1 cells exhibited increased mitochondrial mass and enhanced activity. Electron transport chain complex 1 (ETC1) was rapidly impaired under fever-range temperatures, a phenomenon that was specifically detrimental to T<sub>H</sub>1 cells. T<sub>H</sub>1 cells with elevated DNA damage and ETC1 signatures were also detected in human chronic inflammation. Thus, fever-relevant temperatures disrupt ETC1 to selectively drive apoptosis or adaptation of T<sub>H</sub>1 cells to maintain genomic integrity and enhance effector functions.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adp3475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275856","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}
Duncan M. Morgan, Brendan L. Horton, Vidit Bhandarkar, Richard Van, Teresa Dinter, Maria Zagorulya, J. Christopher Love, Stefani Spranger
{"title":"Expansion of tumor-reactive CD8+ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade","authors":"Duncan M. Morgan, Brendan L. Horton, Vidit Bhandarkar, Richard Van, Teresa Dinter, Maria Zagorulya, J. Christopher Love, Stefani Spranger","doi":"10.1126/sciimmunol.adi3487","DOIUrl":"10.1126/sciimmunol.adi3487","url":null,"abstract":"<div >Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8<sup>+</sup> T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8<sup>+</sup> T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231190","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}
Steven P. Wolf, Matthias Leisegang, Madeline Steiner, Veronika Wallace, Kazuma Kiyotani, Yifei Hu, Leonie Rosenberger, Jun Huang, Karin Schreiber, Yusuke Nakamura, Andrea Schietinger, Hans Schreiber
{"title":"CD4+ T cells with convergent TCR recombination reprogram stroma and halt tumor progression in adoptive therapy","authors":"Steven P. Wolf, Matthias Leisegang, Madeline Steiner, Veronika Wallace, Kazuma Kiyotani, Yifei Hu, Leonie Rosenberger, Jun Huang, Karin Schreiber, Yusuke Nakamura, Andrea Schietinger, Hans Schreiber","doi":"10.1126/sciimmunol.adp6529","DOIUrl":"10.1126/sciimmunol.adp6529","url":null,"abstract":"<div >Cancers eventually kill hosts even when infiltrated by cancer-specific T cells. We examined whether cancer-specific T cell receptors of CD4<sup>+</sup> T cells (CD4TCRs) from tumor-bearing hosts can be exploited for adoptive TCR therapy. We focused on CD4TCRs targeting an autochthonous mutant neoantigen that is only presented by stroma surrounding the MHC class II–negative cancer cells. The 11 most common tetramer-sorted CD4TCRs were tested using TCR-engineered CD4<sup>+</sup> T cells. Three TCRs were characterized by convergent recombination for which multiple T cell clonotypes differed in their nucleotide sequences but encoded identical TCR α and β chains. These preferentially selected TCRs destroyed tumors equally well and halted progression through reprogramming of the tumor stroma. TCRs represented by single T cell clonotypes were similarly effective only if they shared CDR elements with preferentially selected TCRs in both α and β chains. Selecting candidate TCRs on the basis of these characteristics can help identify TCRs that are potentially therapeutically effective.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 99","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231172","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}
Tobias Kammann, Curtis Cai, Takuya Sekine, Elli Mouchtaridi, Caroline Boulouis, Vera Nilsén, Olga Rivera Ballesteros, Thomas R. Müller, Yu Gao, Elisa J. M. Raineri, Akhirunnesa Mily, Sarah Adamo, Christian Constantz, Julia Niessl, Whitney Weigel, Efthymia Kokkinou, Christopher Stamper, Anne Marchalot, John Bassett, Sabrina Ferreira, Inga Rødahl, Nicole Wild, Demi Brownlie, Chris Tibbitt, Jeffrey Y. W. Mak, David P. Fairlie, Edwin Leeansyah, Jakob Michaelsson, Nicole Marquardt, Jenny Mjösberg, Carl Jorns, Marcus Buggert, Johan K. Sandberg
{"title":"MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles","authors":"Tobias Kammann, Curtis Cai, Takuya Sekine, Elli Mouchtaridi, Caroline Boulouis, Vera Nilsén, Olga Rivera Ballesteros, Thomas R. Müller, Yu Gao, Elisa J. M. Raineri, Akhirunnesa Mily, Sarah Adamo, Christian Constantz, Julia Niessl, Whitney Weigel, Efthymia Kokkinou, Christopher Stamper, Anne Marchalot, John Bassett, Sabrina Ferreira, Inga Rødahl, Nicole Wild, Demi Brownlie, Chris Tibbitt, Jeffrey Y. W. Mak, David P. Fairlie, Edwin Leeansyah, Jakob Michaelsson, Nicole Marquardt, Jenny Mjösberg, Carl Jorns, Marcus Buggert, Johan K. Sandberg","doi":"10.1126/sciimmunol.adn2362","DOIUrl":"10.1126/sciimmunol.adn2362","url":null,"abstract":"<div >Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103<sup>+</sup> resident MAIT cells presented an immunoregulatory CD39<sup>high</sup>CD27<sup>low</sup> profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39<sup>high</sup> and hepatic CD56<sup>+</sup> adaptations accumulated with donor age. CD56<sup>+</sup> MAIT cells displayed limited T cell receptor–repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures.</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":"142143376","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}
Andrea Vecchione, Joseph C. Devlin, Carley Tasker, Venkat Raman Ramnarayan, Paul Haase, Eva Conde, Devin Srivastava, Gurinder S. Atwal, Pierre Bruhns, Andrew J. Murphy, Matthew A. Sleeman, Andre Limnander, Wei Keat Lim, Seblewongel Asrat, Jamie M. Orengo
{"title":"IgE plasma cells are transcriptionally and functionally distinct from other isotypes","authors":"Andrea Vecchione, Joseph C. Devlin, Carley Tasker, Venkat Raman Ramnarayan, Paul Haase, Eva Conde, Devin Srivastava, Gurinder S. Atwal, Pierre Bruhns, Andrew J. Murphy, Matthew A. Sleeman, Andre Limnander, Wei Keat Lim, Seblewongel Asrat, Jamie M. Orengo","doi":"10.1126/sciimmunol.adm8964","DOIUrl":"10.1126/sciimmunol.adm8964","url":null,"abstract":"<div >Understanding the phenotypic and transcriptional signature of immunoglobulin E (IgE)–producing cells is fundamental to plasma cell (PC) biology and development of therapeutic interventions for allergy. Here, using a mouse model of intranasal house dust mite (HDM) exposure, we showed that short-lived IgE PCs emerge in lung draining lymph nodes (dLNs) during early exposure (<3 weeks) and long-lived IgE PCs accumulate in the bone marrow (BM) with prolonged exposure (>7 weeks). IgE PCs had distinct surface and gene expression profiles in these different tissues compared with other Ig isotypes. IgE BMPCs up-regulated genes associated with prosurvival and BM homing, whereas IgE dLN PCs expressed genes associated with recent class switching and differentiation. IgE PCs also exhibited higher expression of endoplasmic reticulum (ER) stress and protein coding genes and higher antibody secretion rate when compared with IgG1. Overall, this study highlights the unique developmental path and transcriptional signature of short-lived and long-lived IgE PCs.</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":"https://www.science.org/doi/reader/10.1126/sciimmunol.adm8964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143375","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}
Anna Appios, James Davies, Sofia Sirvent, Stephen Henderson, Sébastien Trzebanski, Johannes Schroth, Morven L. Law, Inês Boal Carvalho, Marlene Magalhaes Pinto, Cyril Carvalho, Howard Yuan-Hao Kan, Shreya Lovlekar, Christina Major, Andres Vallejo, Nigel J. Hall, Michael Ardern-Jones, Zhaoyuan Liu, Florent Ginhoux, Sian M. Henson, Rebecca Gentek, Elaine Emmerson, Steffen Jung, Marta E. Polak, Clare L. Bennett
{"title":"Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity","authors":"Anna Appios, James Davies, Sofia Sirvent, Stephen Henderson, Sébastien Trzebanski, Johannes Schroth, Morven L. Law, Inês Boal Carvalho, Marlene Magalhaes Pinto, Cyril Carvalho, Howard Yuan-Hao Kan, Shreya Lovlekar, Christina Major, Andres Vallejo, Nigel J. Hall, Michael Ardern-Jones, Zhaoyuan Liu, Florent Ginhoux, Sian M. Henson, Rebecca Gentek, Elaine Emmerson, Steffen Jung, Marta E. Polak, Clare L. Bennett","doi":"10.1126/sciimmunol.adp0344","DOIUrl":"10.1126/sciimmunol.adp0344","url":null,"abstract":"<div >Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.</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":"142143374","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":"Pre-vax metabolic clues: Cracking the code to a better dengue vaccine","authors":"Fahima Akther, David R. Martinez","doi":"10.1126/sciimmunol.ads7640","DOIUrl":"10.1126/sciimmunol.ads7640","url":null,"abstract":"<div >Multi-omic analysis deciphers the impact of cell-intrinsic and systemic metabolomes on dengue vaccination immunogenicity.</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":"142143377","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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