William O Hahn, K Rachael Parks, Mingchao Shen, Gabriel Ozorowski, Holly Janes, Lamar Ballweber-Fleming, Amanda S Woodward Davis, Chris Duplessis, Mark Tomai, Antu K Dey, Zachary K Sagawa, Stephen C De Rosa, Aaron Seese, Latha Kallur Siddaramaiah, Leonidas Stamatatos, Wen-Hsin Lee, Leigh M Sewall, Dalton Karlinsey, Hannah L Turner, Vanessa Rubin, Sarah Furth, Kellie MacPhee, Michael Duff, Lawrence Corey, Michael C Keefer, Srilatha Edupuganti, Ian Frank, Janine Maenza, Lindsey R Baden, Ollivier Hyrien, Rogier W Sanders, John P Moore, Andrew B Ward, Georgia D Tomaras, David C Montefiori, Nadine Rouphael, M Juliana McElrath
{"title":"Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.","authors":"William O Hahn, K Rachael Parks, Mingchao Shen, Gabriel Ozorowski, Holly Janes, Lamar Ballweber-Fleming, Amanda S Woodward Davis, Chris Duplessis, Mark Tomai, Antu K Dey, Zachary K Sagawa, Stephen C De Rosa, Aaron Seese, Latha Kallur Siddaramaiah, Leonidas Stamatatos, Wen-Hsin Lee, Leigh M Sewall, Dalton Karlinsey, Hannah L Turner, Vanessa Rubin, Sarah Furth, Kellie MacPhee, Michael Duff, Lawrence Corey, Michael C Keefer, Srilatha Edupuganti, Ian Frank, Janine Maenza, Lindsey R Baden, Ollivier Hyrien, Rogier W Sanders, John P Moore, Andrew B Ward, Georgia D Tomaras, David C Montefiori, Nadine Rouphael, M Juliana McElrath","doi":"10.1084/jem.20240604","DOIUrl":"10.1084/jem.20240604","url":null,"abstract":"<p><p>Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132925","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}
{"title":"Judy Lieberman: Stay curious and excited about science.","authors":"Montserrat Cols","doi":"10.1084/jem.20241556","DOIUrl":"https://doi.org/10.1084/jem.20241556","url":null,"abstract":"Judy Lieberman is a professor of pediatrics and adjunct professor of genetics at Harvard Medical School and an endowed chair in cellular and molecular medicine. Her lab studies cytotoxic T lymphocytes (CTL), key cells in the immune defense against viral infection and cancer, as well as molecular pathways activated by the granzymes, and how RNA interference (RNAi) regulates cell differentiation in health and disease states. We spoke to Judy about advice for early career researchers, how she first become interested in cytotoxic T lymphocytes, and key people who have provided mentorship across her career.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"06 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268578","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":"PTPN2 deficiency: Amping up JAK/STAT.","authors":"Joshua M Tobin, Megan A Cooper","doi":"10.1084/jem.20240980","DOIUrl":"10.1084/jem.20240980","url":null,"abstract":"<p><p>Identification of monogenic causes of immune dysregulation provides insight into human immune response and signaling pathways associated with autoimmunity. Here, Jeanpierre et al. (https://doi.org/10.1084/jem.20232337) identify new germline variants in the gene encoding PTPN2 associated with loss of regulatory function, enhanced JAK/STAT signaling, and early-onset autoimmunity.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727261","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}
Irem Kaymak, McLane J Watson, Brandon M Oswald, Shixin Ma, Benjamin K Johnson, Lisa M DeCamp, Batsirai M Mabvakure, Katarzyna M Luda, Eric H Ma, Kin Lau, Zhen Fu, Brejnev Muhire, Susan M Kitchen-Goosen, Alexandra Vander Ark, Michael S Dahabieh, Bozena Samborska, Matthew Vos, Hui Shen, Zi Peng Fan, Thomas P Roddy, Gillian A Kingsbury, Cristovão M Sousa, Connie M Krawczyk, Kelsey S Williams, Ryan D Sheldon, Susan M Kaech, Dominic G Roy, Russell G Jones
{"title":"ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses.","authors":"Irem Kaymak, McLane J Watson, Brandon M Oswald, Shixin Ma, Benjamin K Johnson, Lisa M DeCamp, Batsirai M Mabvakure, Katarzyna M Luda, Eric H Ma, Kin Lau, Zhen Fu, Brejnev Muhire, Susan M Kitchen-Goosen, Alexandra Vander Ark, Michael S Dahabieh, Bozena Samborska, Matthew Vos, Hui Shen, Zi Peng Fan, Thomas P Roddy, Gillian A Kingsbury, Cristovão M Sousa, Connie M Krawczyk, Kelsey S Williams, Ryan D Sheldon, Susan M Kaech, Dominic G Roy, Russell G Jones","doi":"10.1084/jem.20231820","DOIUrl":"10.1084/jem.20231820","url":null,"abstract":"<p><p>Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that CD8 T cell responses to infection depend on acetyl-CoA derived from citrate via the enzyme ATP citrate lyase (ACLY). However, ablation of ACLY triggers an alternative, acetate-dependent pathway for acetyl-CoA production mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and chromatin accessibility at effector gene loci. When ACLY is functional, ACSS2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, loss of ACLY renders CD8 T cells dependent on acetate (via ACSS2) to maintain acetyl-CoA production and effector function. Together, ACLY and ACSS2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988050","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}
Yi-Hao Chan, Vanja Lundberg, Jérémie Le Pen, Jiayi Yuan, Danyel Lee, Francesca Pinci, Stefano Volpi, Koji Nakajima, Vincent Bondet, Sanna Åkesson, Noopur V Khobrekar, Aaron Bodansky, Likun Du, Tina Melander, Alice-Andrée Mariaggi, Yoann Seeleuthner, Tariq Shikh Saleh, Debanjana Chakravarty, Per Marits, Kerry Dobbs, Sofie Vonlanthen, Viktoria Hennings, Karolina Thörn, Darawan Rinchai, Lucy Bizien, Matthieu Chaldebas, Ali Sobh, Tayfun Özçelik, Sevgi Keles, Suzan A AlKhater, Carolina Prando, Isabelle Meyts, Michael R Wilson, Jérémie Rosain, Emmanuelle Jouanguy, Mélodie Aubart, Laurent Abel, Trine H Mogensen, Qiang Pan-Hammarström, Daxing Gao, Darragh Duffy, Aurélie Cobat, Stefan Berg, Luigi D Notarangelo, Oliver Harschnitz, Charles M Rice, Lorenz Studer, Jean-Laurent Casanova, Olov Ekwall, Shen-Ying Zhang
{"title":"SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.","authors":"Yi-Hao Chan, Vanja Lundberg, Jérémie Le Pen, Jiayi Yuan, Danyel Lee, Francesca Pinci, Stefano Volpi, Koji Nakajima, Vincent Bondet, Sanna Åkesson, Noopur V Khobrekar, Aaron Bodansky, Likun Du, Tina Melander, Alice-Andrée Mariaggi, Yoann Seeleuthner, Tariq Shikh Saleh, Debanjana Chakravarty, Per Marits, Kerry Dobbs, Sofie Vonlanthen, Viktoria Hennings, Karolina Thörn, Darawan Rinchai, Lucy Bizien, Matthieu Chaldebas, Ali Sobh, Tayfun Özçelik, Sevgi Keles, Suzan A AlKhater, Carolina Prando, Isabelle Meyts, Michael R Wilson, Jérémie Rosain, Emmanuelle Jouanguy, Mélodie Aubart, Laurent Abel, Trine H Mogensen, Qiang Pan-Hammarström, Daxing Gao, Darragh Duffy, Aurélie Cobat, Stefan Berg, Luigi D Notarangelo, Oliver Harschnitz, Charles M Rice, Lorenz Studer, Jean-Laurent Casanova, Olov Ekwall, Shen-Ying Zhang","doi":"10.1084/jem.20231725","DOIUrl":"10.1084/jem.20231725","url":null,"abstract":"<p><p>Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633619","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}
Timothy A Watkins, Alex B Green, Julien A R Amat, Nagarjuna R Cheemarla, Katrin Hänsel, Richard Lozano, Sarah N Dudgeon, Gregory Germain, Marie L Landry, Wade L Schulz, Ellen F Foxman
{"title":"High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children.","authors":"Timothy A Watkins, Alex B Green, Julien A R Amat, Nagarjuna R Cheemarla, Katrin Hänsel, Richard Lozano, Sarah N Dudgeon, Gregory Germain, Marie L Landry, Wade L Schulz, Ellen F Foxman","doi":"10.1084/jem.20230911","DOIUrl":"10.1084/jem.20230911","url":null,"abstract":"<p><p>Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1β and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468425","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}
Zhoujie Ding, Nicola Laura Diny, Rebecca Gentek, Shiri Gur-Cohen, Motoko Y Kimura, Hui-Fern Koay, Giuliana Magri, Araceli Perez-Lopez, Natalia Barbara Pikor, Lauren B Rodda
{"title":"Women in STEM becoming independent: Embrace failures as part of the journey to success.","authors":"Zhoujie Ding, Nicola Laura Diny, Rebecca Gentek, Shiri Gur-Cohen, Motoko Y Kimura, Hui-Fern Koay, Giuliana Magri, Araceli Perez-Lopez, Natalia Barbara Pikor, Lauren B Rodda","doi":"10.1084/jem.20241219","DOIUrl":"10.1084/jem.20241219","url":null,"abstract":"","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855650","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}
{"title":"B cell tolerance and autoimmunity: Lessons from repertoires.","authors":"Jacques Deguine, Ramnik J Xavier","doi":"10.1084/jem.20231314","DOIUrl":"10.1084/jem.20231314","url":null,"abstract":"<p><p>Adaptive immune cell function is regulated by a highly diverse receptor recombined from variable germline-encoded segments that can recognize an almost unlimited array of epitopes. While this diversity enables the recognition of any pathogen, it also poses a risk of self-recognition, leading to autoimmunity. Many layers of regulation are present during both the generation and activation of B cells to prevent this phenomenon, although they are evidently imperfect. In recent years, our ability to analyze immune repertoires at scale has drastically increased, both through advances in sequencing and single-cell analyses. Here, we review the current knowledge on B cell repertoire analyses, focusing on their implication for autoimmunity. These studies demonstrate that a failure of tolerance occurs at multiple independent checkpoints in different autoimmune contexts, particularly during B cell maturation, plasmablast differentiation, and within germinal centers. These failures are marked by distinct repertoire features that may be used to identify disease- or patient-specific therapeutic approaches.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874991","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}
Erika Valeri, Sara Breggion, Federica Barzaghi, Monah Abou Alezz, Giovanni Crivicich, Isabel Pagani, Federico Forneris, Claudia Sartirana, Matteo Costantini, Stefania Costi, Achille Marino, Eleonora Chiarotto, Davide Colavito, Rolando Cimaz, Ivan Merelli, Elisa Vicenzi, Alessandro Aiuti, Anna Kajaste-Rudnitski
{"title":"A novel STING variant triggers endothelial toxicity and SAVI disease.","authors":"Erika Valeri, Sara Breggion, Federica Barzaghi, Monah Abou Alezz, Giovanni Crivicich, Isabel Pagani, Federico Forneris, Claudia Sartirana, Matteo Costantini, Stefania Costi, Achille Marino, Eleonora Chiarotto, Davide Colavito, Rolando Cimaz, Ivan Merelli, Elisa Vicenzi, Alessandro Aiuti, Anna Kajaste-Rudnitski","doi":"10.1084/jem.20232167","DOIUrl":"10.1084/jem.20232167","url":null,"abstract":"<p><p>Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report and characterize a novel STING variant (F269S) identified in a SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation of interferon (IFN) and inflammatory pathways across cell types and a striking prevalence of circulating naïve T cells was observed. Inducible STING F269S expression conferred enhanced signaling through ligand-independent translocation of the protein to the Golgi, protecting cells from viral infections but preventing their efficient immune priming. Additionally, endothelial cell activation was promoted and further exacerbated by cytokine secretion by SAVI immune cells, resulting in inflammation and endothelial damage. Our findings identify STING F269S mutation as a novel pathogenic variant causing SAVI, highlight the importance of the crosstalk between endothelial and immune cells in the context of lung disease, and contribute to a better understanding of how aberrant STING activation can cause pathology.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492234","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}
{"title":"The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.","authors":"Mark Esposito, John K Amory, Yibin Kang","doi":"10.1084/jem.20240519","DOIUrl":"10.1084/jem.20240519","url":null,"abstract":"<p><p>The retinoid nuclear receptor pathway, activated by the vitamin A metabolite retinoic acid, has been extensively investigated for over a century. This study has resulted in conflicting hypotheses about how the pathway regulates health and how it should be pharmaceutically manipulated. These disagreements arise from a fundamental contradiction: retinoid agonists offer clear benefits to select patients with rare bone growth disorders, acute promyelocytic leukemia, and some dermatologic diseases, yet therapeutic retinoid pathway activation frequently causes more harm than good, both through acute metabolic dysregulation and a delayed cancer-promoting effect. In this review, we discuss controlled clinical, mechanistic, and genetic data to suggest several disease settings where inhibition of the retinoid pathway may be a compelling therapeutic strategy, such as solid cancers or metabolic syndromes, and also caution against continued testing of retinoid agonists in cancer patients. Considerable evidence suggests a central role for retinoid regulation of immunity and metabolism, with therapeutic opportunities to antagonize retinoid signaling proposed in cancer, diabetes, and obesity.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 9","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916831","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}
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