Pub Date : 2026-02-10DOI: 10.1038/s41590-026-02429-2
Arwaf S. Alharbi, Sunil Sapkota, Zhikuan Zhang, Ruitao Jin, Erandi Rupasinghe, W. Samantha N. Jayasekara, Dingyi Yu, Mary Speir, Lorna Wilkinson-White, Liza Cubeddu, Julia I. Ellyard, Refaya Rezwan, Daniel S. Wenholz, Alexandra L. McAllan, Rui Gao, Le Ying, Rasan M. Sathiqu, Hani Hosseini Far, Josiah Bones, Sitong He, Marina R. Alexander, Kim A. Lennox, Paul J. Hertzog, Claudia A. Nold-Petry, Cameron R. Stewart, Carola G. Vinuesa, Mark A. Behlke, Umeharu Ohto, Olivier F. Laczka, Roland Gamsjaeger, Ben Corry, Toshiyuki Shimizu, Michael P. Gantier
Recognition of RNA fragments by Toll-like receptor 7 (TLR7) and TLR8 helps to initiate the innate immune response against pathogens. An outstanding question is why RNA fragments generated during clearance of apoptotic cells fail to activate TLR7 and TLR8 signaling. Here we show that select 2′-O-methyl (2′-OMe) guanosine RNA fragments, including those derived from host RNAs, function as potent TLR7 and TLR8 antagonists and reduce TLR7 sensing in vivo. Mechanistically, these fragments bind to an antagonistic site on these proteins via their 5′-end 2′-OMe guanosine. These findings indicate that host RNAs evade detection because abundant ribosomal 2′-OMe-modified fragments naturally antagonize TLR7 and TLR8. Crucially, rare TLR7 and TLR8 mutations at this antagonist binding site decrease inhibition by 2′-OMe guanosine RNA fragments, leading to autoimmunity in patients. Collectively, this work redefines TLR7 and TLR8 sensing by introducing 2′-OMe guanosine as a natural immune checkpoint for their activation.
{"title":"2′-O-Methyl-guanosine RNA fragments antagonize TLR7 and TLR8 to limit autoimmunity","authors":"Arwaf S. Alharbi, Sunil Sapkota, Zhikuan Zhang, Ruitao Jin, Erandi Rupasinghe, W. Samantha N. Jayasekara, Dingyi Yu, Mary Speir, Lorna Wilkinson-White, Liza Cubeddu, Julia I. Ellyard, Refaya Rezwan, Daniel S. Wenholz, Alexandra L. McAllan, Rui Gao, Le Ying, Rasan M. Sathiqu, Hani Hosseini Far, Josiah Bones, Sitong He, Marina R. Alexander, Kim A. Lennox, Paul J. Hertzog, Claudia A. Nold-Petry, Cameron R. Stewart, Carola G. Vinuesa, Mark A. Behlke, Umeharu Ohto, Olivier F. Laczka, Roland Gamsjaeger, Ben Corry, Toshiyuki Shimizu, Michael P. Gantier","doi":"10.1038/s41590-026-02429-2","DOIUrl":"https://doi.org/10.1038/s41590-026-02429-2","url":null,"abstract":"Recognition of RNA fragments by Toll-like receptor 7 (TLR7) and TLR8 helps to initiate the innate immune response against pathogens. An outstanding question is why RNA fragments generated during clearance of apoptotic cells fail to activate TLR7 and TLR8 signaling. Here we show that select 2′-O-methyl (2′-OMe) guanosine RNA fragments, including those derived from host RNAs, function as potent TLR7 and TLR8 antagonists and reduce TLR7 sensing in vivo. Mechanistically, these fragments bind to an antagonistic site on these proteins via their 5′-end 2′-OMe guanosine. These findings indicate that host RNAs evade detection because abundant ribosomal 2′-OMe-modified fragments naturally antagonize TLR7 and TLR8. Crucially, rare TLR7 and TLR8 mutations at this antagonist binding site decrease inhibition by 2′-OMe guanosine RNA fragments, leading to autoimmunity in patients. Collectively, this work redefines TLR7 and TLR8 sensing by introducing 2′-OMe guanosine as a natural immune checkpoint for their activation.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"45 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10DOI: 10.1038/s41590-026-02430-9
Nicholas J. Maurice, Talia S. Dalzell, Trevor N. Tankersley, Ka Hyun Rhee, Katharine E. Block, Nicholas N. Jarjour, Taylor A. DePauw, Sarah M. Wall, Sara E. Hamilton, Stephen C. Jameson
Memory CD8+ T (Tmem) cells are activated into innate-like killers by cytokines, including interleukin-12 (IL-12), IL-15 and IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are unclear. Here we show that basal IL-4 signals antagonize IL-18 sensing and subsequent interferon-γ production during Tmem cell bystander activation. IL-4 treatment can act directly on Tmem cells in a STAT6-dependent manner to limit interferon-γ-mediated control of a bystander bacterial infection. IL-4 does not simply block bystander activation but tunes effector molecule expression. Strain-specific defects in bystander activation of homeostatic Tmem cells partially relates to IL-4 exposure, but these differences are erased in Tmem cells produced by T cell antigen receptor activation, leading to uniform IL-18 receptor expression and capacity for bystander activation/cytotoxicity. Our data demonstrate that bystander activation by inflammatory cytokines is subject to regulation by both IL-4 and prior antigen experience. These findings underscore the importance of the cytokine milieu in dictating bystander-mediated pathogen control.
记忆性CD8+ T （Tmem）细胞被白细胞介素-12 （IL-12）、IL-15和IL-18等细胞因子激活为先天类杀手；但调节这种现象的机制（称为旁观者激活）尚不清楚。本研究表明，在Tmem细胞旁观者激活过程中，基础IL-4信号可拮抗IL-18感应和随后的干扰素-γ产生。IL-4治疗可以以stat6依赖的方式直接作用于Tmem细胞，以限制干扰素-γ介导的旁观者细菌感染的控制。IL-4不是简单地阻断旁观者的激活，而是调节效应分子的表达。稳态Tmem细胞旁观者激活的菌株特异性缺陷部分与IL-4暴露有关，但这些差异在T细胞抗原受体激活产生的Tmem细胞中被消除，导致IL-18受体表达和旁观者激活/细胞毒性能力一致。我们的数据表明，炎症细胞因子的旁观者激活受到IL-4和先前抗原经验的调节。这些发现强调了细胞因子环境在决定旁观者介导的病原体控制中的重要性。
{"title":"IL-4–STAT6 signaling delays protective CD8+ T cell bystander activation by antagonizing IL-18 sensing","authors":"Nicholas J. Maurice, Talia S. Dalzell, Trevor N. Tankersley, Ka Hyun Rhee, Katharine E. Block, Nicholas N. Jarjour, Taylor A. DePauw, Sarah M. Wall, Sara E. Hamilton, Stephen C. Jameson","doi":"10.1038/s41590-026-02430-9","DOIUrl":"https://doi.org/10.1038/s41590-026-02430-9","url":null,"abstract":"Memory CD8+ T (Tmem) cells are activated into innate-like killers by cytokines, including interleukin-12 (IL-12), IL-15 and IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are unclear. Here we show that basal IL-4 signals antagonize IL-18 sensing and subsequent interferon-γ production during Tmem cell bystander activation. IL-4 treatment can act directly on Tmem cells in a STAT6-dependent manner to limit interferon-γ-mediated control of a bystander bacterial infection. IL-4 does not simply block bystander activation but tunes effector molecule expression. Strain-specific defects in bystander activation of homeostatic Tmem cells partially relates to IL-4 exposure, but these differences are erased in Tmem cells produced by T cell antigen receptor activation, leading to uniform IL-18 receptor expression and capacity for bystander activation/cytotoxicity. Our data demonstrate that bystander activation by inflammatory cytokines is subject to regulation by both IL-4 and prior antigen experience. These findings underscore the importance of the cytokine milieu in dictating bystander-mediated pathogen control.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10DOI: 10.1038/s41590-026-02419-4
Junyun Lai, Cheok Weng Chan, Jesse D. Armitage, Katherine M. Audsley, Yu-Kuan Huang, Emily B. Derrick, Laura S. Carstensen, Christina M. Scheffler, Matt E. Jones, Kevin Sek, Nicola Principe, Joelle S. Kim, Imran G. House, Amanda X. Y. Chen, Kah Min Yap, Jim Middelburg, Isabelle Munoz, Dat Nguyen, Junming Tong, Thang X. Hoang, Kirsten L. Todd, Maximilien Evrard, Jonathan Chee, Laura K. Mackay, Alistair R. R. Forrest, Ian A. Parish, Anthony Bosco, Jason Waithman, Paul A. Beavis, Phillip K. Darcy
Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (TPEX), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. Here we show that treatment with Fms-related tyrosine kinase 3 ligand (Flt3L) expands CD62L+SLAMF6+CD8+ T cells in the tumor through a mechanism that requires XCR1+ dendritic cells to traffic to the tumor-draining lymph node. The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8+ T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8+ T cells within tumors through a mechanism that is dependent on lymph node egress.
{"title":"Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T cells in lymph nodes","authors":"Junyun Lai, Cheok Weng Chan, Jesse D. Armitage, Katherine M. Audsley, Yu-Kuan Huang, Emily B. Derrick, Laura S. Carstensen, Christina M. Scheffler, Matt E. Jones, Kevin Sek, Nicola Principe, Joelle S. Kim, Imran G. House, Amanda X. Y. Chen, Kah Min Yap, Jim Middelburg, Isabelle Munoz, Dat Nguyen, Junming Tong, Thang X. Hoang, Kirsten L. Todd, Maximilien Evrard, Jonathan Chee, Laura K. Mackay, Alistair R. R. Forrest, Ian A. Parish, Anthony Bosco, Jason Waithman, Paul A. Beavis, Phillip K. Darcy","doi":"10.1038/s41590-026-02419-4","DOIUrl":"https://doi.org/10.1038/s41590-026-02419-4","url":null,"abstract":"Immune checkpoint blockade (ICB) evokes antitumor immunity through the reinvigoration of T cell responses. T cell differentiation status controls response, with less differentiated cells having an enhanced capacity to proliferate after ICB. Given that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted T cells (TPEX), we hypothesized that expansion of cDC1s with Flt3L could enhance responses to ICB. Here we show that treatment with Fms-related tyrosine kinase 3 ligand (Flt3L) expands CD62L+SLAMF6+CD8+ T cells in the tumor through a mechanism that requires XCR1+ dendritic cells to traffic to the tumor-draining lymph node. The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8+ T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8+ T cells within tumors through a mechanism that is dependent on lymph node egress.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"89 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1038/s41590-026-02446-1
Mikhail B Litinskiy, Bernardetta Nardelli, David M Hilbert, Bing He, Andras Schaffer, Paolo Casali, Andrea Cerutti
{"title":"Retraction Note: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL.","authors":"Mikhail B Litinskiy, Bernardetta Nardelli, David M Hilbert, Bing He, Andras Schaffer, Paolo Casali, Andrea Cerutti","doi":"10.1038/s41590-026-02446-1","DOIUrl":"https://doi.org/10.1038/s41590-026-02446-1","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1038/s41590-025-02398-y
Vasileios I Theofilou, David Fraser, Eleni Kanasi, Laurie Brenchley, Teresa Greenwell-Wild, Emmanuel E Adade, Alex M Valm, Iyadh Douagi, Yasmine Belkaid, Duy T Tran, Drake W Williams, Niki M Moutsopoulos
Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.
{"title":"Distinct spatial organization governs oral mucosal immunity.","authors":"Vasileios I Theofilou, David Fraser, Eleni Kanasi, Laurie Brenchley, Teresa Greenwell-Wild, Emmanuel E Adade, Alex M Valm, Iyadh Douagi, Yasmine Belkaid, Duy T Tran, Drake W Williams, Niki M Moutsopoulos","doi":"10.1038/s41590-025-02398-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02398-y","url":null,"abstract":"<p><p>Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1038/s41590-026-02449-y
Jayashree Srinivasan, Colin R Moore, Aparna Calindi, Bryan R Helm, Yilin Yang, John F Moore, Hilary J Selden, Cody N Heiser, Qi Liu, Ken S Lau, Lauren I R Ehrlich
{"title":"Publisher Correction: The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct thymocyte cell types.","authors":"Jayashree Srinivasan, Colin R Moore, Aparna Calindi, Bryan R Helm, Yilin Yang, John F Moore, Hilary J Selden, Cody N Heiser, Qi Liu, Ken S Lau, Lauren I R Ehrlich","doi":"10.1038/s41590-026-02449-y","DOIUrl":"https://doi.org/10.1038/s41590-026-02449-y","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1038/s41590-025-02412-3
Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Joanna Dreux, Alaina K Cagalingan, Florian Schustek, Lena Flood, Tamson Moore, Lisa L Kirkemo, Isabelle J Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, Claire D Clelland, Leah Sibener, Bruce A C Cree, Stephen L Hauser, Jill A Hollenbach, Marvin Gee, Michael R Wilson, Scott S Zamvil, Joseph J Sabatino
CD8+ T cells are the dominant clonally expanded lymphocyte population in multiple sclerosis (MS) lesions but their clonal identity, function and antigen specificity are not well understood. A comprehensive single-cell RNA-sequencing and T cell receptor-sequencing analysis of the cerebrospinal fluid and blood from individuals in the MS and control cohorts revealed a subset of 23 highly expanded and activated CD8+ T cell clonotypes that were enriched predominantly in the cerebrospinal fluid in the MS cohort. Using unbiased and targeted antigen discovery approaches, six CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. Although the majority of mimotopes did not elicit functional responses, three of the expanded CD8+ T cell receptors from patients with MS were reactive to EBV. EBV DNA and transcripts were detected in cerebrospinal fluid, including in patients with MS who had highly expanded EBV-specific CD8+ T cells. These findings shed vital insight into the role of CD8+ T cells in MS and support an important role of EBV in MS immunopathology.
{"title":"Antigen specificity of clonally enriched CD8<sup>+</sup> T cells in multiple sclerosis.","authors":"Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Joanna Dreux, Alaina K Cagalingan, Florian Schustek, Lena Flood, Tamson Moore, Lisa L Kirkemo, Isabelle J Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, Claire D Clelland, Leah Sibener, Bruce A C Cree, Stephen L Hauser, Jill A Hollenbach, Marvin Gee, Michael R Wilson, Scott S Zamvil, Joseph J Sabatino","doi":"10.1038/s41590-025-02412-3","DOIUrl":"10.1038/s41590-025-02412-3","url":null,"abstract":"<p><p>CD8<sup>+</sup> T cells are the dominant clonally expanded lymphocyte population in multiple sclerosis (MS) lesions but their clonal identity, function and antigen specificity are not well understood. A comprehensive single-cell RNA-sequencing and T cell receptor-sequencing analysis of the cerebrospinal fluid and blood from individuals in the MS and control cohorts revealed a subset of 23 highly expanded and activated CD8<sup>+</sup> T cell clonotypes that were enriched predominantly in the cerebrospinal fluid in the MS cohort. Using unbiased and targeted antigen discovery approaches, six CD8<sup>+</sup> T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. Although the majority of mimotopes did not elicit functional responses, three of the expanded CD8<sup>+</sup> T cell receptors from patients with MS were reactive to EBV. EBV DNA and transcripts were detected in cerebrospinal fluid, including in patients with MS who had highly expanded EBV-specific CD8<sup>+</sup> T cells. These findings shed vital insight into the role of CD8<sup>+</sup> T cells in MS and support an important role of EBV in MS immunopathology.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1038/s41590-025-02415-0
Adelaide Gelineau, Brian D Brown, Edward J Hall, Lucy L Wang, Ronald N Germain, Christophe Benoist
{"title":"Immunological knowledge.","authors":"Adelaide Gelineau, Brian D Brown, Edward J Hall, Lucy L Wang, Ronald N Germain, Christophe Benoist","doi":"10.1038/s41590-025-02415-0","DOIUrl":"https://doi.org/10.1038/s41590-025-02415-0","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1038/s41590-025-02414-1
Arundhoti Das, Yi Ding, Christelle Harly, Avinash Bhandoola
Innate lymphoid cells (ILCs) are a diverse group of immune cells that possess many effector functions of T cells but lack somatically generated receptors. They have crucial roles in early immune responses and in maintaining tissue integrity. We review ILC developmental pathways and progenitors in mice, with a particular focus on adult bone marrow but also addressing fetal liver. We present recent insights into the earliest steps of ILC specification, as well as new evidence for developmental pathways that generate two functionally distinct types of natural killer cells. The anatomical locations where ILC progenitors are identified are outlined and evidence supporting ILC development in tissues examined. In addition, key transcriptional regulators that support ILC development are discussed. Although ILC and T-lineage cells use many of the same transcriptional controllers during development, we present new evidence indicating ILC transcriptional programs diverge from T-lineage programs at the earliest known steps of ILC lineage specification.
{"title":"The development of innate lymphoid cells.","authors":"Arundhoti Das, Yi Ding, Christelle Harly, Avinash Bhandoola","doi":"10.1038/s41590-025-02414-1","DOIUrl":"https://doi.org/10.1038/s41590-025-02414-1","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are a diverse group of immune cells that possess many effector functions of T cells but lack somatically generated receptors. They have crucial roles in early immune responses and in maintaining tissue integrity. We review ILC developmental pathways and progenitors in mice, with a particular focus on adult bone marrow but also addressing fetal liver. We present recent insights into the earliest steps of ILC specification, as well as new evidence for developmental pathways that generate two functionally distinct types of natural killer cells. The anatomical locations where ILC progenitors are identified are outlined and evidence supporting ILC development in tissues examined. In addition, key transcriptional regulators that support ILC development are discussed. Although ILC and T-lineage cells use many of the same transcriptional controllers during development, we present new evidence indicating ILC transcriptional programs diverge from T-lineage programs at the earliest known steps of ILC lineage specification.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113461","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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