Nature Immunology最新文献

Six degrees of TGFβ 6度TGFβ

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02201-y

Quinn Peters, Martin Prlic

引用次数: 0

Restoring balanced HSC youth 恢复平衡的HSC青春

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02250-3

Laurie A. Dempsey

{"title":"Restoring balanced HSC youth","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02250-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02250-3","url":null,"abstract":"Hematopoietic stem cells (HSCs) in aged individuals become less functional in their regenerative potential and biased towards myeloid cell output with reduced lymphoid and erythroid cell production. In Nature Aging, Sun et al. investigate the cell-intrinsic mechanism that underlies skewed myelopoiesis in aged HSCs. Comparing transcriptional differences between HSCs from young and old mice, the authors identified candidate genes that were subsequently targeted by CRISPR-mediated mutagenesis in HSCs from old Cas9 mice. This screen identified Cd38 and Clu (encoding clusterin), with the latter shown to be a key driver of myeloid production bias in aged HSCs. Loss of clusterin led to more balanced lymphoid-myeloid cell output and increased long-term reconstitution potential. Mechanistically, cytosolic clusterin associates with mitochondria proteins TOM20 and MFN2, leading to increased mitochondrial hyperfusion as well as reduced mitophagy. Higher expression of Clu or Cd38 caused excessive mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, increased DNA damage and activation of the p38 MAPK pathway in aged HSCs. The clusterin-dependent increase in mito-ROS and phosphorylated p-p38 increased the expression and activity of the transcription factor CEBPB, resulting in myeloid-biased lineage differentiation of aged HSC progeny cells.Original reference: Nat. Aging https://doi.org/10.1038/s43587-025-00908-z (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736784","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}

引用次数: 0

Mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis 乳腺上皮内淋巴细胞和肠道输入形成乳发生中的T细胞动力学

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02218-3

Abigail Jaquish, Eleni Phung, Xutong Gong, Pilar Baldominos, Silvia Galván-Peña, Ian Magill, Isabelle Bursulaya, Eleonora Marina, Kerri Bertrand, Christina Chambers, Andrés R. Muñoz-Rojas, Judith Agudo, Diane Mathis, Christophe Benoist, Deepshika Ramanan

{"title":"Mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis","authors":"Abigail Jaquish, Eleni Phung, Xutong Gong, Pilar Baldominos, Silvia Galván-Peña, Ian Magill, Isabelle Bursulaya, Eleonora Marina, Kerri Bertrand, Christina Chambers, Andrés R. Muñoz-Rojas, Judith Agudo, Diane Mathis, Christophe Benoist, Deepshika Ramanan","doi":"10.1038/s41590-025-02218-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02218-3","url":null,"abstract":"Pregnancy brings about profound changes in the mammary gland to prepare for lactation, yet immunocyte changes that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells, revealing a marked increase in CD4+ and CD8+ T effector cells, including an expansion of T cell receptor (TCR)αβ+CD8αα+ cells, in pregnancy and lactation. T cells were localized in the mammary epithelium, resembling intraepithelial lymphocytes (IELs) typically found in mucosal tissues. Similarity to mucosal tissues was substantiated by demonstrating partial dependence on microbial cues, T cell migration from the intestine to the mammary gland in late pregnancy and shared TCR clonotypes between intestinal and mammary tissues, including intriguing public TCR families. Putative counterparts of mammary IELs were found in human breast and milk. Mammary IELs are thus poised to manage the transition from a nonmucosal tissue to a mucosal barrier during lactogenesis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736772","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}

引用次数: 0

PD-1 is requisite for skin TRM cell formation and specification by TGFβ PD-1是皮肤TRM细胞形成和TGFβ规范所必需的

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02228-1

K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy

{"title":"PD-1 is requisite for skin TRM cell formation and specification by TGFβ","authors":"K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy","doi":"10.1038/s41590-025-02228-1","DOIUrl":"https://doi.org/10.1038/s41590-025-02228-1","url":null,"abstract":"Tissue-resident memory T (TRM) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. TRM cells are implicated in autoimmunity, successful response to immune checkpoint blockade in the tumor microenvironment and toxicities that occur after immune checkpoint blockade in peripheral tissues. Here, we identified that signaling through the immune checkpoint programmed death receptor 1 (PD-1) strongly impacts the early specification of CD8+ TRM cells in the skin. PD-1 is expressed broadly across mouse and human skin TRM cells, in the absence of persistent infection, and is retained on skin TRM cells in aged mice. PD-1 supports early TRM cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin TRM cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"1 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736773","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}

引用次数: 0

Targeting CAFs 针对战乱国家

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02248-x

Nicholas J. Bernard

引用次数: 0

Intraepithelial T cells move from gut to breast to shape lactation 上皮内T细胞从肠道转移到乳房形成泌乳

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02221-8

Amanpreet Singh Chawla, Mahima Swamy

引用次数: 0

The immunology of asthma 哮喘的免疫学

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02212-9

Bart N. Lambrecht, Engi Ahmed, Hamida Hammad

引用次数: 0

Anti-tumor immunity is boosted by loss of TGFβ-driven tissue residency 抗肿瘤免疫通过tgf β驱动的组织驻留的丧失而增强

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02224-5

Dongmei Zhao, Hai-Hui Xue

引用次数: 0

Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity 淋巴结衍生的干细胞样而非肿瘤组织驻留的CD8+ T细胞可促进抗癌免疫

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02219-2

Sharanya K. M. Wijesinghe, Lisa Rausch, Sarah S. Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D. Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R. Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D. Huntington, Thomas Gebhardt, Daniel T. Utzschneider, Marco J. Herold, Wei Shi, Jan Schroeder, Enrico Lugli, Axel Kallies

{"title":"Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity","authors":"Sharanya K. M. Wijesinghe, Lisa Rausch, Sarah S. Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D. Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R. Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D. Huntington, Thomas Gebhardt, Daniel T. Utzschneider, Marco J. Herold, Wei Shi, Jan Schroeder, Enrico Lugli, Axel Kallies","doi":"10.1038/s41590-025-02219-2","DOIUrl":"https://doi.org/10.1038/s41590-025-02219-2","url":null,"abstract":"CD8+ T cell-mediated tumor control and efficacy of immune checkpoint blockade (ICB) are associated with both precursors of exhausted T (TPEX) cells and tissue-resident memory T cells. Their relationships and relative contribution to tumor control, however, are insufficiently understood. Using single-cell RNA sequencing and genetic mouse models, we systematically dissected the heterogeneity and function of cytotoxic T cells in tumors and tumor-draining lymph nodes (tdLNs). We found that intratumoral TCF1+ TPEX cells and their progeny acquired a tissue-residency program that limits their contribution to tumor control and ICB response. By contrast, MYB-dependent stem-like TPEX cells residing in tdLNs sustained CD8+ T cell infiltration into tumors and mediated ICB response. The cytokine TGFβ was the central factor that enforced residency of intratumoral CD8+ T cells and limited the abundance of stem-like TPEX cells in tdLNs, thereby restraining tumor control. A similar network of TGFβ-constrained intratumoral and extratumoral CD8+ T cells with precursor and residency characteristics was found in human cancer.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"24 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736774","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}

引用次数: 0

Carboxylation switch 羧化作用开关

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02249-w

Ioana Staicu

{"title":"Carboxylation switch","authors":"Ioana Staicu","doi":"10.1038/s41590-025-02249-w","DOIUrl":"https://doi.org/10.1038/s41590-025-02249-w","url":null,"abstract":"Activation of mitochondrial antiviral signaling protein (MAVS) at the mitochondria membrane mediates both interferon (IFN) and apoptosis responses. In Science, Okazaki et al. show that carboxylation of MAVS enhances type I IFN responses and represses apoptosis. MAVS was carboxylated at residues Asp53, Glu70, Glu80 and Asp83 in its cytoplasmic domain, and knockdown of γ-glutamyl carboxylase (GGCX), a type II endoplasmic reticulum (ER) transmembrane protein that carboxylates extracellular or ER lumen proteins in a manner dependent on the GGCX cofactor vitamin K, reduced MAVS carboxylation. MAVS activation was associated with increased accumulation of a non-glycosylated, inverted GGCX protein at the ER membrane. Expression of carboxylation-mutant MAVS, deletion of GGCX or inhibition of vitamin K decreased IFNβ and increased caspase-3 in response to viral infection. The mitochondrial transport protein TOMM40 and the kinase PLK1 associated with carboxylation-mutant MAVS, but not wild-type MAVS, and increased caspase-3, but not IFNβ. Deletion of GGCX in neural, but not myeloid cells, and vitamin K inhibition or deficiency in mice infected with vesicular stomatitis virus (VSV) reduced type I IFN and increased VSV titers and caspase-3 activation in the brain of wild-type, but not MAVS-deficient mice. Thus, GGCX carboxylation of MAVS acts as a regulatory switch in virus-infected cells.Original reference: Science https://doi.org/10.1126/science.adk9967 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"126 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736799","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}

引用次数: 0