Josephine Elena Reek, Constantin M. Zohner, Gabriel Reuben Smith, Susan C. Cook-Patton, Pieter De Frenne, Paolo D’Odorico, Marius G. Floriancic, Robert B. Jackson, Julia A. Jones, James W. Kirchner, Marysa Laguë, Yuting Liang, Yuta J. Masuda, Robert I. McDonald, Luke A. Parsons, Benedict S. Probst, June T. Spector, Thales A. P. West, Nicholas H. Wolff, Florian Zellweger, Thomas W. Crowther
Forests regulate global and local climates in ways that impact human well-being. In this Review, we discuss the scale-dependent mechanisms through which forests regulate climate, highlighting their contributions to global mitigation and local adaptation. Locally, forests tend to buffer temperatures, cooling in warm conditions and warming in cold ones. In regions that naturally support dense forest cover, trees contribute to global cooling primarily through carbon uptake, with some offsetting from albedo-related warming. By enhancing rainfall interception, evapotranspiration, and cloud formation, forests also influence the hydrological cycle, lowering flood risks in humid regions but often reducing downstream water availability, especially in drier climates. Collectively, these interacting processes show that the greatest climate benefits occur where forests are native, highlighting their importance for both climate adaptation and mitigation.
{"title":"More than mitigation: The role of forests in climate adaptation","authors":"Josephine Elena Reek, Constantin M. Zohner, Gabriel Reuben Smith, Susan C. Cook-Patton, Pieter De Frenne, Paolo D’Odorico, Marius G. Floriancic, Robert B. Jackson, Julia A. Jones, James W. Kirchner, Marysa Laguë, Yuting Liang, Yuta J. Masuda, Robert I. McDonald, Luke A. Parsons, Benedict S. Probst, June T. Spector, Thales A. P. West, Nicholas H. Wolff, Florian Zellweger, Thomas W. Crowther","doi":"10.1126/science.ads4361","DOIUrl":"10.1126/science.ads4361","url":null,"abstract":"<div >Forests regulate global and local climates in ways that impact human well-being. In this Review, we discuss the scale-dependent mechanisms through which forests regulate climate, highlighting their contributions to global mitigation and local adaptation. Locally, forests tend to buffer temperatures, cooling in warm conditions and warming in cold ones. In regions that naturally support dense forest cover, trees contribute to global cooling primarily through carbon uptake, with some offsetting from albedo-related warming. By enhancing rainfall interception, evapotranspiration, and cloud formation, forests also influence the hydrological cycle, lowering flood risks in humid regions but often reducing downstream water availability, especially in drier climates. Collectively, these interacting processes show that the greatest climate benefits occur where forests are native, highlighting their importance for both climate adaptation and mitigation.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jared W. Westbrook, Joanna Malukiewicz, Qian Zhang, Avinash Sreedasyam, Jerry W. Jenkins, Vasiliy Lakoba, Sara Fitzsimmons, Jamie Van Clief, Kendra Collins, Stephen Hoy, Cassie Stark, Lake Graboski, Eric Jenkins, Thomas M. Saielli, Benjamin T. Jarrett, Lucinda J. Wigfield, Lauren M. Kerwien, Ciera Wilbur, Alexander M. Sandercock, J. Hill Craddock, Susanna Keriö, Tetyana Zhebentyayeva, Shenghua Fan, Austin M. Thomas, Albert G. Abbott, C. Dana Nelson, Xiaoxia Xia, James R. McKenna, Caleb Kell, Melissa Williams, LoriBeth Boston, Christopher Plott, Florian Carle, Jack Swatt, Jack Ostroff, Steven N. Jeffers, Kathleen McKeever, Erica Smith, Thomas J. Ellis, Joseph B. James, Paul Sisco, Andrew Newhouse, Erik Carlson, William A. Powell, Frederick V. Hebard, John Scrivani, Caragh Heverly, Martin Cipollini, Brian Clark, Eric Evans, Bruce Levine, John E. Carlson, David Goodstein, Jack Orebaugh, Zamin K. Yang, Madhavi Z. Martin, Joanna Tannous, Tomás A. Rush, Nancy L. Engle, Timothy J. Tschaplinski, Jane Grimwood, Jeremy Schmutz, Jason A. Holliday, John T. Lovell
More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. However, progress has been slow because of the complex genetic architecture of resistance. To better understand blight resistance, we compared reference genomes, gene expression responses, and stem metabolite profiles of the resistant Chinese and susceptible American chestnut species. To accelerate resistance breeding, we conducted large-scale phenotyping and genotyping in hybrids of these species. Simulation and inoculation experiments suggest that significant resistance gains are possible through selectively breeding trees with an average of 70 to 85% American chestnut ancestry. The resources developed in this work are foundational for breeding to create diverse restoration populations with sufficient disease resistance and competitive growth.
{"title":"Genomic approaches to accelerate American chestnut restoration","authors":"Jared W. Westbrook, Joanna Malukiewicz, Qian Zhang, Avinash Sreedasyam, Jerry W. Jenkins, Vasiliy Lakoba, Sara Fitzsimmons, Jamie Van Clief, Kendra Collins, Stephen Hoy, Cassie Stark, Lake Graboski, Eric Jenkins, Thomas M. Saielli, Benjamin T. Jarrett, Lucinda J. Wigfield, Lauren M. Kerwien, Ciera Wilbur, Alexander M. Sandercock, J. Hill Craddock, Susanna Keriö, Tetyana Zhebentyayeva, Shenghua Fan, Austin M. Thomas, Albert G. Abbott, C. Dana Nelson, Xiaoxia Xia, James R. McKenna, Caleb Kell, Melissa Williams, LoriBeth Boston, Christopher Plott, Florian Carle, Jack Swatt, Jack Ostroff, Steven N. Jeffers, Kathleen McKeever, Erica Smith, Thomas J. Ellis, Joseph B. James, Paul Sisco, Andrew Newhouse, Erik Carlson, William A. Powell, Frederick V. Hebard, John Scrivani, Caragh Heverly, Martin Cipollini, Brian Clark, Eric Evans, Bruce Levine, John E. Carlson, David Goodstein, Jack Orebaugh, Zamin K. Yang, Madhavi Z. Martin, Joanna Tannous, Tomás A. Rush, Nancy L. Engle, Timothy J. Tschaplinski, Jane Grimwood, Jeremy Schmutz, Jason A. Holliday, John T. Lovell","doi":"10.1126/science.adw3225","DOIUrl":"10.1126/science.adw3225","url":null,"abstract":"<div >More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. However, progress has been slow because of the complex genetic architecture of resistance. To better understand blight resistance, we compared reference genomes, gene expression responses, and stem metabolite profiles of the resistant Chinese and susceptible American chestnut species. To accelerate resistance breeding, we conducted large-scale phenotyping and genotyping in hybrids of these species. Simulation and inoculation experiments suggest that significant resistance gains are possible through selectively breeding trees with an average of 70 to 85% American chestnut ancestry. The resources developed in this work are foundational for breeding to create diverse restoration populations with sufficient disease resistance and competitive growth.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L-Carnitine (the form of carnitine found in animals) transports long-chain fatty acids into mitochondria, where they go through β-oxidation, producing energy (1). This process occurs primarily in organs that use fat as energy, such as cardiac and skeletal muscles. For humans who eat meat, most carnitine is obtained from food. However, ~25% of the supply of carnitine in omnivorous humans relies on de novo synthesis, which reaches >90% among strict vegetarians or vegans. Endogenous carnitine is synthesized in the liver and kidneys from two methylated amino acids, lysine and methionine (1). This requires the transfer of trimethyllysine from the cytosol to the mitochondrial matrix (the innermost part of the mitochondria), for conversion into hydroxytrimethyllysine (2). On page 688 of this issue, Auger et al. (3) report that a mitochondrial trimethyllysine transporter, SLC25A45, has a key role in fat consumption in mice.
{"title":"The bottleneck of fat burning","authors":"Angela M. Ramos-Lobo, Pierre Maechler","doi":"10.1126/science.aef2173","DOIUrl":"10.1126/science.aef2173","url":null,"abstract":"<div >L-Carnitine (the form of carnitine found in animals) transports long-chain fatty acids into mitochondria, where they go through β-oxidation, producing energy (<i>1</i>). This process occurs primarily in organs that use fat as energy, such as cardiac and skeletal muscles. For humans who eat meat, most carnitine is obtained from food. However, ~25% of the supply of carnitine in omnivorous humans relies on de novo synthesis, which reaches >90% among strict vegetarians or vegans. Endogenous carnitine is synthesized in the liver and kidneys from two methylated amino acids, lysine and methionine (<i>1</i>). This requires the transfer of trimethyllysine from the cytosol to the mitochondrial matrix (the innermost part of the mitochondria), for conversion into hydroxytrimethyllysine (<i>2</i>). On page 688 of this issue, Auger <i>et al.</i> (<i>3</i>) report that a mitochondrial trimethyllysine transporter, SLC25A45, has a key role in fat consumption in mice.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Organisms have developed a variety of mechanisms to cope with potentially harmful mutations. These mechanisms include gene duplication, redundancy of metabolic factors or pathways, and feedback loops, all of which create backup systems and hidden reserves that ensure cellular stability (1). On page 687 of this issue, El-Brolosy et al. (2) report on transcriptional adaptation, a dual feedback and feedforward mechanism that uses genetic redundancy to compensate for mutations in protein-coding genes. The authors report that cells transport decay fragments of mutant messenger RNAs (mRNAs) from the cytoplasm to the nucleus to up-regulate the transcription of so-called “adapting genes”—the mutated gene; its paralogs (genes that originated from the same duplication event); and, in some cases, biologically related genes. El-Brolosy et al. also leveraged their mechanistic understanding of transcriptional regulation to develop short nucleic acid sequences that can artificially activate target gene expression in cells.
{"title":"Keeping cells fit","authors":"Xavier Rambout, Lynne E. Maquat","doi":"10.1126/science.aee7910","DOIUrl":"10.1126/science.aee7910","url":null,"abstract":"<div >Organisms have developed a variety of mechanisms to cope with potentially harmful mutations. These mechanisms include gene duplication, redundancy of metabolic factors or pathways, and feedback loops, all of which create backup systems and hidden reserves that ensure cellular stability (<i>1</i>). On page 687 of this issue, El-Brolosy <i>et al</i>. (<i>2</i>) report on transcriptional adaptation, a dual feedback and feedforward mechanism that uses genetic redundancy to compensate for mutations in protein-coding genes. The authors report that cells transport decay fragments of mutant messenger RNAs (mRNAs) from the cytoplasm to the nucleus to up-regulate the transcription of so-called “adapting genes”—the mutated gene; its paralogs (genes that originated from the same duplication event); and, in some cases, biologically related genes. El-Brolosy <i>et al</i>. also leveraged their mechanistic understanding of transcriptional regulation to develop short nucleic acid sequences that can artificially activate target gene expression in cells.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA comes close to copying itself","authors":"Robert F. Service","doi":"10.1126/science.aeg3559","DOIUrl":"10.1126/science.aeg3559","url":null,"abstract":"","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dredging and mining river sediments can raise flood risks and threaten infrastructure, scientists say.
科学家说，疏浚和开采河流沉积物会增加洪水风险，并威胁到基础设施。
{"title":"Projects on silty Himalayan rivers raise alarms.","authors":"Athar Parvaiz","doi":"10.1126/science.aeg3558","DOIUrl":"https://doi.org/10.1126/science.aeg3558","url":null,"abstract":"<p><p>Dredging and mining river sediments can raise flood risks and threaten infrastructure, scientists say.</p>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":"644-645"},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donia Arafa, Julia van de Korput, Philipp N. Braaker, Kieran P. Higgins, Niels R. C. Meijns, Katy L. H. Marshall-Phelps, Julia Meng, Daniel Soong, Eleonora Scalia, Kyle Lathem, Marcus Keatinge, Claire Richmond, Anna Klingseisen, Marja Main, Sarah A. Neely, David W. Hampton, Greg J. Duncan, Geert J. Schenk, Marie Louise Groot, Siddharthan Chandran, Ben Emery, Antonio Luchicchi, Maarten H. P. Kole, Anna C. Williams, David A. Lyons
Myelin damage is a hallmark of several neurological disorders, but how it occurs remains to be fully understood. In this study, we found that early damage in zebrafish and rodent demyelination models is characterized by myelin swelling. We show, through live imaging, that myelin swelling does not always lead to myelin loss and that swellings can sometimes resolve, allowing sheaths to remodel. Increased neuronal activity during early demyelination exacerbates myelin damage, whereas reducing neuronal activity mitigates myelin swelling in both zebrafish and mice. In human multiple sclerosis tissue, myelin swelling is also dynamic and is prominent around active lesions. Our data indicate that myelin swelling is a conserved feature of demyelination and that damage to myelin sheaths can resolve, opening opportunities for targeting human disease.
{"title":"Myelin sheaths in the central nervous system can withstand damage and dynamically remodel","authors":"Donia Arafa, Julia van de Korput, Philipp N. Braaker, Kieran P. Higgins, Niels R. C. Meijns, Katy L. H. Marshall-Phelps, Julia Meng, Daniel Soong, Eleonora Scalia, Kyle Lathem, Marcus Keatinge, Claire Richmond, Anna Klingseisen, Marja Main, Sarah A. Neely, David W. Hampton, Greg J. Duncan, Geert J. Schenk, Marie Louise Groot, Siddharthan Chandran, Ben Emery, Antonio Luchicchi, Maarten H. P. Kole, Anna C. Williams, David A. Lyons","doi":"10.1126/science.adr4661","DOIUrl":"10.1126/science.adr4661","url":null,"abstract":"<div >Myelin damage is a hallmark of several neurological disorders, but how it occurs remains to be fully understood. In this study, we found that early damage in zebrafish and rodent demyelination models is characterized by myelin swelling. We show, through live imaging, that myelin swelling does not always lead to myelin loss and that swellings can sometimes resolve, allowing sheaths to remodel. Increased neuronal activity during early demyelination exacerbates myelin damage, whereas reducing neuronal activity mitigates myelin swelling in both zebrafish and mice. In human multiple sclerosis tissue, myelin swelling is also dynamic and is prominent around active lesions. Our data indicate that myelin swelling is a conserved feature of demyelination and that damage to myelin sheaths can resolve, opening opportunities for targeting human disease.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fangyuan Xiong, Zhongyang Li, Sébastien Brosse, Julian D. Olden, Steven J. Cooke, Bo Yang, Ying Lu, Wenqi Gao, Wei Xin, Yushun Chen
China’s rapid economic development has triggered an unparalleled freshwater biodiversity crisis since the 1950s. To restore fisheries resources, the Yangtze River Fishing Ban was implemented in 2021 to cease all basin-wide commercial fishing. We evaluate the effectiveness of this large-scale conservation action by assessing fish communities across mainstem habitats before and after the ban (2018 to 2023). The seven-decadal biodiversity loss was halted with improvements in fish biomass, body condition, species diversity, and initial recovery of threatened species. Eliminating fishing pressure was likely key to this recovery, in addition to actions targeting water quality improvement, hydrological and riparian habitat restoration, and vessel traffic reduction. Ambitious conservation actions can halt biodiversity loss in the Yangtze River, bringing hope for biodiversity recovery in other large rivers.
{"title":"Fishing ban halts seven decades of biodiversity decline in the Yangtze River","authors":"Fangyuan Xiong, Zhongyang Li, Sébastien Brosse, Julian D. Olden, Steven J. Cooke, Bo Yang, Ying Lu, Wenqi Gao, Wei Xin, Yushun Chen","doi":"10.1126/science.adu5160","DOIUrl":"10.1126/science.adu5160","url":null,"abstract":"<div >China’s rapid economic development has triggered an unparalleled freshwater biodiversity crisis since the 1950s. To restore fisheries resources, the Yangtze River Fishing Ban was implemented in 2021 to cease all basin-wide commercial fishing. We evaluate the effectiveness of this large-scale conservation action by assessing fish communities across mainstem habitats before and after the ban (2018 to 2023). The seven-decadal biodiversity loss was halted with improvements in fish biomass, body condition, species diversity, and initial recovery of threatened species. Eliminating fishing pressure was likely key to this recovery, in addition to actions targeting water quality improvement, hydrological and riparian habitat restoration, and vessel traffic reduction. Ambitious conservation actions can halt biodiversity loss in the Yangtze River, bringing hope for biodiversity recovery in other large rivers.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas M. Adams, Daniel Martinez-Krams, Eduardo Esteva, Ai C. Ra, Allegra Iliadi Alexiou, Hua Jin, Tae Jin Yun, Rayan Sleiman Tellaoui, Tenny Mudianto, Emily Vollmer, Ekaterina Novikova, Yanjun Tan, William Huntley, Oleg Krichevsky, Igor Dolgalev, Peter Izmirly, Jill P. Buyon, Andre L. Moreira, Amanda W. Lund, Boris Reizis
Dendritic cells (DCs) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DCs, including tissue-derived migratory DCs (migDCs), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T (Treg) cells, spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)–like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg cell abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DCs and implicate it in the regulation of human autoimmunity.
{"title":"Transcription factor Etv3 controls the tolerogenic function of dendritic cells","authors":"Nicholas M. Adams, Daniel Martinez-Krams, Eduardo Esteva, Ai C. Ra, Allegra Iliadi Alexiou, Hua Jin, Tae Jin Yun, Rayan Sleiman Tellaoui, Tenny Mudianto, Emily Vollmer, Ekaterina Novikova, Yanjun Tan, William Huntley, Oleg Krichevsky, Igor Dolgalev, Peter Izmirly, Jill P. Buyon, Andre L. Moreira, Amanda W. Lund, Boris Reizis","doi":"10.1126/science.ads1246","DOIUrl":"10.1126/science.ads1246","url":null,"abstract":"<div >Dendritic cells (DCs) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DCs, including tissue-derived migratory DCs (migDCs), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25<sup>low</sup> regulatory T (T<sub>reg</sub>) cells, spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)–like disease, supporting the reported genetic association of human <i>ETV3</i> with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the T<sub>reg</sub> cell abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DCs and implicate it in the regulation of human autoimmunity.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brenna C. Remick, Joshua Q. Mao, Andrew G. Manford, Ami D. Gutierrez-Jensen, Allon Wagner, Michael Rape, Grant McFadden, Masmudur M. Rahman, Moritz M. Gaidt, Russell E. Vance
Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors.” To discover ETI pathways in mammals, we developed a screening approach in which we expressed individual virulence factors in a human monocyte cell line and assessed transcriptional responses by RNA sequencing. We identified a poxvirus effector, myxoma virus M3.1, which elicited an antiviral nuclear factor κB (NF-κB) response. NF-κB was unleashed by an ETI pathway that sensed M3.1 attack of two antiviral complexes: zinc finger antiviral protein and TBK1. NF-κΒ activation occurred because the proteins inhibited by M3.1—N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-κB. Our study established a systematic approach for the discovery of ETI pathways, and the results illustrated how negative regulators of immune responses may function in pathogen sensing.
{"title":"Poxvirus attack of antiviral defense pathways unleashes an effector-triggered NF-κB response","authors":"Brenna C. Remick, Joshua Q. Mao, Andrew G. Manford, Ami D. Gutierrez-Jensen, Allon Wagner, Michael Rape, Grant McFadden, Masmudur M. Rahman, Moritz M. Gaidt, Russell E. Vance","doi":"10.1126/science.adw4937","DOIUrl":"10.1126/science.adw4937","url":null,"abstract":"<div >Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors.” To discover ETI pathways in mammals, we developed a screening approach in which we expressed individual virulence factors in a human monocyte cell line and assessed transcriptional responses by RNA sequencing. We identified a poxvirus effector, myxoma virus M3.1, which elicited an antiviral nuclear factor κB (NF-κB) response. NF-κB was unleashed by an ETI pathway that sensed M3.1 attack of two antiviral complexes: zinc finger antiviral protein and TBK1. NF-κΒ activation occurred because the proteins inhibited by M3.1—N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-κB. Our study established a systematic approach for the discovery of ETI pathways, and the results illustrated how negative regulators of immune responses may function in pathogen sensing.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"391 6786","pages":""},"PeriodicalIF":45.8,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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