Nature Immunology最新文献_第5页

Treg cells control female nociception Treg细胞控制女性的伤害感觉

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02160-4

Stephanie Houston

{"title":"Treg cells control female nociception","authors":"Stephanie Houston","doi":"10.1038/s41590-025-02160-4","DOIUrl":"https://doi.org/10.1038/s41590-025-02160-4","url":null,"abstract":"Women experience a higher prevalence of chronic pain, and pain hypersensitivity has been observed in female mice, but that mechanisms that drive sexual dimorphism in nociception remain unclear. In Science, Midavaine et al. find that meningeal regulatory T (mTreg) cells controlled the responses of female mice to mechanical pain via the endogenous opioid peptide enkephalin. Intrathecal injection of pegylated diphtheria toxin to Foxp3-DTR mice enabled the selective depletion of mTreg cells, which resulted in decreased mechanical nociceptive thresholds in female, but not male mice. Conversely, intrathecal injection of low-dose IL-2 led to mTreg cell expansion, and this increased the nociceptive threshold in female, but not male mice. Blocking female sex hormones prevented the mTreg cell expansion-mediated increases in the nociceptive threshold. mTreg cells expressed Penk, which encodes proenkephalin, a precursor of analgesic enkephalin peptides. In female mic, the expansion of mTreg cells resulted in increased levels of enkephalin in the cerebrospinal fluid. During nerve injury, enkephalin decreased pain sensing by activating δ-opioid receptors expressed by sensory neurons. Thus, in female mice, mTreg cells have an important role in controlling the activation of sensory neurons in response to mechanical pain.Original reference: Science https://doi.org/10.1126/science.adq6531 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"45 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893164","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

Skin–gut crosstalk

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02158-y

Nicholas J. Bernard

{"title":"Skin–gut crosstalk","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02158-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02158-y","url":null,"abstract":"Skin damage can have systemic effects but whether it can result in the priming of immune responses that are spatially removed from the skin is less clear. Data now published in Science Immunology show that cytokines released from damaged skin can function as endocrine adjuvants to prime normally tolerogenic gastrointestinal immune responses to the model food antigen ovalbumin, thereby driving humoral responses in mice. This ‘remote priming’ was demonstrated by oral gavage of ovalbumin in combination with tape stripping to damage the skin and resulted in ovalbumin-specific antibody responses. The same allergic sensitization was shown by two other means of acute skin damage (punch biopsy or intradermal acetone injection), a model of chronic atopic dermatitis (using calcipotriol) and in response to ultraviolet radiation damage. Although the cytokine signatures varied with the different skin damage methods, the researchers used cytokine immunizations and various cell-specific knockout mice to show that the cytokines IL-33 and TSLP were sufficient to drive similar ovalbumin-specific antibody responses to skin damage, in part by activation of group 2 innate lymphoid cells.Original reference: Sci. Immunol. 10, eadn0688 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"16 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893197","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

Gut T cell plasticity generates pathogenic TFH cells that promote systemic autoimmunity 肠道T细胞可塑性产生致病性TFH细胞，促进全身自身免疫

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02147-1

引用次数: 0

Identification of soluble biomarkers that associate with distinct manifestations of long COVID 与新冠肺炎不同表现相关的可溶性生物标志物的鉴定

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02135-5

Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S. Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A. Jones, Per Julin, Christer Lidman, Richard J. Stanton, Paul A. Goepfert, Michael J. Peluso, Steven G. Deeks, Helen E. Davies, Soo Aleman, Marcus Buggert, David A. Price

{"title":"Identification of soluble biomarkers that associate with distinct manifestations of long COVID","authors":"Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S. Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A. Jones, Per Julin, Christer Lidman, Richard J. Stanton, Paul A. Goepfert, Michael J. Peluso, Steven G. Deeks, Helen E. Davies, Soo Aleman, Marcus Buggert, David A. Price","doi":"10.1038/s41590-025-02135-5","DOIUrl":"https://doi.org/10.1038/s41590-025-02135-5","url":null,"abstract":"Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8+ T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"195 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893198","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

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

引用次数: 0

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}

引用次数: 0

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

引用次数: 0

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}

引用次数: 0

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

引用次数: 0