Nature Immunology最新文献_第2页

Evolving Rel 进化Rel

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02142-6

Myong-Hee Sung, Ranjan Sen

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Stepwise neofunctionalization of the NF-κB family member Rel during vertebrate evolution NF-κB家族成员Rel在脊椎动物进化过程中的逐步新功能化

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02138-2

Allison E. Daly, Abraham B. Chang, Prabhat K. Purbey, Kevin J. Williams, Shuxing Li, Benjamin D. Redelings, George Yeh, Yongqing Wu, Scott D. Pope, Byrappa Venkatesh, Sibon Li, Kaylin Nguyen, Joseph Rodrigues, Kelsey Jorgensen, Ananya Dasgupta, Trevor Siggers, Lin Chen, Stephen T. Smale

{"title":"Stepwise neofunctionalization of the NF-κB family member Rel during vertebrate evolution","authors":"Allison E. Daly, Abraham B. Chang, Prabhat K. Purbey, Kevin J. Williams, Shuxing Li, Benjamin D. Redelings, George Yeh, Yongqing Wu, Scott D. Pope, Byrappa Venkatesh, Sibon Li, Kaylin Nguyen, Joseph Rodrigues, Kelsey Jorgensen, Ananya Dasgupta, Trevor Siggers, Lin Chen, Stephen T. Smale","doi":"10.1038/s41590-025-02138-2","DOIUrl":"https://doi.org/10.1038/s41590-025-02138-2","url":null,"abstract":"Adaptive immunity and the five vertebrate NF-κB family members first emerged in cartilaginous fish, suggesting that NF-κB family divergence helped to facilitate adaptive immunity. One specialized function of the NF-κB Rel protein in macrophages is activation of Il12b, which encodes a key regulator of T cell development. We found that Il12b exhibits much greater Rel dependence than inducible innate immunity genes in macrophages, with the unique function of Rel dimers depending on a heightened intrinsic DNA-binding affinity. Chromatin immunoprecipitation followed by sequencing experiments defined differential DNA-binding preferences of NF-κB family members genome-wide, and X-ray crystallography revealed a key residue that supports the heightened DNA-binding affinity of Rel dimers. Unexpectedly, this residue, the heightened affinity of Rel dimers, and the portion of the Il12b promoter bound by Rel dimers were largely restricted to mammals. Our findings reveal major structural transitions in an NF-κB family member and one of its key target promoters at a late stage of vertebrate evolution that apparently contributed to immunoregulatory rewiring in mammalian species.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"223 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893282","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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Unravelling the interplay between respiratory disease and the immune landscape in long COVID 揭示呼吸道疾病与长期COVID免疫景观之间的相互作用

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02140-8

James A. Harker, Ryan S. Thwaites

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Short-range immunity 短程免疫力

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02157-z

Ioana Staicu

{"title":"Short-range immunity","authors":"Ioana Staicu","doi":"10.1038/s41590-025-02157-z","DOIUrl":"https://doi.org/10.1038/s41590-025-02157-z","url":null,"abstract":"The double-stranded RNA (dsRNA) sensor 2′,5′-oligoadenylate synthetase (OAS) produces the linear oligonucleotide 2-5A, which binds to and activates RNase L to cleave host and viral RNA and activate RIG-I-like receptors. In Immunity, Yan and colleagues show that 2-5A is transferred from cell to cell through gap junctions to mediate short-range communication between cells during infection and cancer. RNase L-knockout A549 cells treated with poly(I:C) activate RNA cleavage in OAS-knockout A549 cells, whereas A549 cells expressing a constitutively active OAS induce IFN and ISG expression in wild-type but not in RNase L-knockdown mouse embryonic fibroblasts, both in a manner dependent on the connexins CX43 and CX45, which form gap junctions. Most cell types produce 2-5A after treatment with IFN or poly(I:C) and some also export it to the extracellular space. Extracellular 2-5A is imported in cells through the same transporters as the cyclic dinucleotide cGAMP. In culture, cells that can produce, export and import 2-5A have better control of VSV viral infection. In a model of MC38 cells implanted subcutaneously into C56BL/6 mice, MC38 cells that cannot make or export 2-5A or MC38 cells implanted in Rnasel−/−, Rag1−/− or Ifnar1−/− mice grow faster than their wild-type counterparts. Expression of OAS correlates positively with the level of CD8+ T cell infiltration and better survival in human cancer.Original reference: Immunity 58, 797–810 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"15 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893161","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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Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity 肠道内TH17细胞可塑性产生的异常T滤泡辅助细胞促进肠外自身免疫

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02125-7

Tingting Fan, Chi Tai, Kiah C. Sleiman, Madeline P. Cutcliffe, Haram Kim, Ye Liu, Jianying Li, Gang Xin, Mollyanna Grashel, Laurie Baert, Chinwe Ekeocha, Paige Vergenes, Svetlana Lima, Wan-Lin Lo, Judith Lin, Beatriz Hanaoka, Trevor N. Tankersley, Min Wang, Xuan Zhang, George C. Tsokos, Wael Jarjour, Randy Longman, Hsin-Jung Joyce Wu

{"title":"Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity","authors":"Tingting Fan, Chi Tai, Kiah C. Sleiman, Madeline P. Cutcliffe, Haram Kim, Ye Liu, Jianying Li, Gang Xin, Mollyanna Grashel, Laurie Baert, Chinwe Ekeocha, Paige Vergenes, Svetlana Lima, Wan-Lin Lo, Judith Lin, Beatriz Hanaoka, Trevor N. Tankersley, Min Wang, Xuan Zhang, George C. Tsokos, Wael Jarjour, Randy Longman, Hsin-Jung Joyce Wu","doi":"10.1038/s41590-025-02125-7","DOIUrl":"https://doi.org/10.1038/s41590-025-02125-7","url":null,"abstract":"Much remains unknown regarding T follicular helper 17 (TFH17) cells commonly found in autoimmune patients. We previously showed that (and here ask why) egress of gut segmented filamentous bacteria (SFB)-induced TFH cells from Peyer’s patches (PP) to systemic sites promotes arthritis. We found splenic TFH17 cells are gut derived. Functional analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced TH17-to-TFH cell reprogramming that dominantly occurs in PPs. Unlike conventional TFH cells, TH17-derived TFH cells are highly migratory and atypically concentrated in the dark zone of germinal centers (GCs). Compared to conventional TFH cells, TH17-derived TFH cells express higher levels of TFH-associated functional molecules and more robustly conjugate with B cells. Gain- and loss-of-function studies demonstrated their dominance in promoting GC B cells and arthritis. Notably, murine gut TH17-derived TFH signatures exist in rheumatoid arthritis patients. Thus, gut T cell plasticity generates atypical, potent TFH cells promoting systemic autoimmunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"24 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893200","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

Cholinergic T cells revitalize the tumor immune microenvironment: TIME to ChAT 胆碱能T细胞激活肿瘤免疫微环境：时间到了

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02144-4

Chunxing Zheng, Shaofeng Liu, Nastaran Fazel Modares, Michael St. Paul, Tak W. Mak

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Acetylcholine-secreting B cells constrain macrophage responses to influenza virus 分泌乙酰胆碱的B细胞抑制巨噬细胞对流感病毒的反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-29 DOI: 10.1038/s41590-025-02148-0

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Interferon-β treatment restores myeloid function and reverses immunosuppression in sepsis 干扰素-β治疗可恢复脓毒症患者的骨髓功能并逆转免疫抑制

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-23 DOI: 10.1038/s41590-025-02143-5

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Endothelium calls macrophages for destruction 内皮细胞呼叫巨噬细胞进行破坏

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-22 DOI: 10.1038/s41590-025-02123-9

Emmanuel L. Gautier

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B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine B细胞通过神经递质乙酰胆碱调节肺部抗病毒炎症反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-22 DOI: 10.1038/s41590-025-02124-8

Antonio Cembellin-Prieto, Zheng Luo, Heather Kulaga, Nicole Baumgarth

{"title":"B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine","authors":"Antonio Cembellin-Prieto, Zheng Luo, Heather Kulaga, Nicole Baumgarth","doi":"10.1038/s41590-025-02124-8","DOIUrl":"https://doi.org/10.1038/s41590-025-02124-8","url":null,"abstract":"The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling the infection. In the present study, we identified acetylcholine (ACh)-producing B cells as such early regulators. B cells are the most prevalent ACh-producing leukocyte population in the respiratory tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before and after infection with influenza A virus. Mice lacking ChAT in B cells, disabling their ability to generate ACh (ChatBKO), but not those lacking ChAT in T cells, significantly, selectively and directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, but not alveolar, macrophage activation and their ability to secrete tumor necrosis factor (TNF), while better controlling virus replication at 1 d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased viral loads at that time. By day 10 of infection, ChatBKO mice showed increased local and systemic inflammation and reduced signs of lung epithelial repair despite similar viral loads and viral clearance. Thus, B cells are key participants of an immediate early regulatory cascade that controls lung tissue damage after viral infection, shifting the balance toward reduced inflammation at the cost of enhanced early viral replication.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"6 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857505","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