Nature Immunology最新文献

Physiological microbial exposure normalizes memory T cell surveillance of the brain and modifies host seizure outcomes 生理微生物暴露使记忆T细胞对大脑的监视正常化，并改变宿主癫痫发作的结果

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-13 DOI: 10.1038/s41590-025-02174-y

Madison R. Mix, Benjamin L. Kreitlow, Roger R. Berton, Julie Xu, Cori E. Fain, Stephanie van de Wall, Lecia L. Pewe, Lisa S. Hancox, Mariah A. Hassert, Shravan Kumar Kannan, Sahaana A. Arumugam, Cassie M. Sievers, Gordon F. Buchanan, Thomas S. Griffith, Vladimir P. Badovinac, John T. Harty

{"title":"Physiological microbial exposure normalizes memory T cell surveillance of the brain and modifies host seizure outcomes","authors":"Madison R. Mix, Benjamin L. Kreitlow, Roger R. Berton, Julie Xu, Cori E. Fain, Stephanie van de Wall, Lecia L. Pewe, Lisa S. Hancox, Mariah A. Hassert, Shravan Kumar Kannan, Sahaana A. Arumugam, Cassie M. Sievers, Gordon F. Buchanan, Thomas S. Griffith, Vladimir P. Badovinac, John T. Harty","doi":"10.1038/s41590-025-02174-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02174-y","url":null,"abstract":"Recent studies have highlighted the presence of memory T cells in human brains, some of which are specific for peripheral infections. To address their potential origins, we used two models of polymicrobial exposure to ‘normalize’ the immune systems of specific pathogen-free mice and queried the impact on brain T cell biology. Here, we show that cohousing and sequential infection induce marked enhancement of memory T cells in the brain tissue of mice. These resident and circulating memory T cells localized to diverse brain regions where dynamic interactions with myeloid cells occurred. Following an induced seizure, brain-localized memory T cells were functionally altered in microbe-experienced mice. Microbial exposure also induced T cell-dependent changes in seizure duration. These data not only suggest a potential origin for memory T cells in human brains but also reveal the ability of these cells to modulate brain biology, prompting the future utilization of microbe-experienced mice in studies of neurological health and disease.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"42 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278579","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

Cathepsin L-dependent positive selection shapes clonal composition and functional fitness of CD4+ T cells 组织蛋白酶l依赖的阳性选择决定了CD4+ T细胞的克隆组成和功能适应性

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-13 DOI: 10.1038/s41590-025-02182-y

Elisabetta Petrozziello, Amina Sayed, João A. Freitas, Christine Federle, Jelena Nedjic, Sarina Ravens, Batuhan Akçabozan, Anna M. Schulz, Dietmar Zehn, Marc Schmidt-Supprian, Reinhard Obst, Immo Prinz, Martijn Verdoes, Jan Kisielow, Thomas Reinheckel, Tobias Straub, Stephen R. Daley, Ludger Klein

{"title":"Cathepsin L-dependent positive selection shapes clonal composition and functional fitness of CD4+ T cells","authors":"Elisabetta Petrozziello, Amina Sayed, João A. Freitas, Christine Federle, Jelena Nedjic, Sarina Ravens, Batuhan Akçabozan, Anna M. Schulz, Dietmar Zehn, Marc Schmidt-Supprian, Reinhard Obst, Immo Prinz, Martijn Verdoes, Jan Kisielow, Thomas Reinheckel, Tobias Straub, Stephen R. Daley, Ludger Klein","doi":"10.1038/s41590-025-02182-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02182-y","url":null,"abstract":"The physiological significance of thymic positive selection and its reliance on a single stromal cell type, cortical thymic epithelial cells, remain incompletely understood. The lysosomal cysteine protease cathepsin L (CTSL) has been implicated in generating major histocompatibility complex class II-bound peptides in cortical thymic epithelial cells for efficient CD4+ T cell differentiation. Here, we addressed the extent and nature of the CD4+ T cell repertoire changes associated with CTSL deficiency. In the absence of CTSL, a highly selective loss of T cell receptors resulted in a markedly reduced repertoire diversity. However, a similarly large proportion of nominally ‘CTSL-independent’ T cell receptors were retained. Clones representative of the second category experienced weaker positive selection signals in the absence of CTSL, which were sufficient for further maturation yet imprinted aberrant responsiveness to agonist stimulation and impaired homeostatic behavior. Together, these findings demonstrate that CTSL is crucial for both shaping full repertoire diversity and optimizing CD4+ T cell functionality.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"1 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278617","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

Let the CAThepsin L out of the thymus 把组织蛋白酶L从胸腺里放出来

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-13 DOI: 10.1038/s41590-025-02173-z

Nuno L. Alves

引用次数: 0

The BCR-SEQC initiative BCR-SEQC倡议

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-13 DOI: 10.1038/s41590-025-02196-6

Rittika Mallik, Rebecca Kusko, Andrea C. Baines, Reena Philip, Marc R. Theoret, Eline T. Luning Prak, Wenming Xiao

{"title":"The BCR-SEQC initiative","authors":"Rittika Mallik, Rebecca Kusko, Andrea C. Baines, Reena Philip, Marc R. Theoret, Eline T. Luning Prak, Wenming Xiao","doi":"10.1038/s41590-025-02196-6","DOIUrl":"https://doi.org/10.1038/s41590-025-02196-6","url":null,"abstract":"B cells express a diverse repertoire of antigen receptors known as B cell receptors (BCRs). BCR proteins are composed of two identical heavy chains (IGH) and two identical light chains (IGK or IGL). BCR diversity is generated by V(D)J recombination, assembling V, D and J gene segments for the heavy chain or V and J segments for the light chain. Further diversification occurs via nucleotide addition and deletion at junctions between the recombining gene segments. The third complementarity-determining region (CDR3) of IGH is the most diverse part of the BCR and serves as a clonal marker. After BCR assembly in the bone marrow, B cells migrate to peripheral lymphoid organs to participate in immune responses. Here, BCRs undergo further modification by somatic hypermutation (SHM) and class-switch recombination (for example, from IgM to IgG, IgA or IgE). These processes refine BCR specificity and function1.Adaptive immune receptor repertoire profiling (AIRR-seq) is performed by next-generation sequencing of BCR and T cell receptor (TCR) gene rearrangements2. AIRR-seq can evaluate hundreds to billions of antigen receptors per individual. Profiling blood, bone marrow or lymph node samples can reveal B cell clones associated with responses to vaccines, self (autoimmunity), or sizable expansions linked to lymphoid malignancies. Longitudinal sampling further enables the study of clonal recruitment and intraclonal diversification in response to specific antigens.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278513","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

Resistance to anti-PD-1 therapy is driven by CD30+ regulatory T cell activity 抗pd -1治疗的耐药性是由CD30+调节性T细胞活性驱动的

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-10 DOI: 10.1038/s41590-025-02175-x

引用次数: 0

Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment 靶向乳酸化增强NK细胞在肿瘤微环境中的细胞毒性

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-10 DOI: 10.1038/s41590-025-02178-8

Jing Jin, Peidong Yan, Dongyao Wang, Lin Bai, Hao Liang, Xiaoyu Zhu, Huaiping Zhu, Chen Ding, Haiming Wei, Yi Wang

引用次数: 0

CAR T cells affect cognition CAR - T细胞影响认知

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-02 DOI: 10.1038/s41590-025-02188-6

Paula Jauregui

{"title":"CAR T cells affect cognition","authors":"Paula Jauregui","doi":"10.1038/s41590-025-02188-6","DOIUrl":"https://doi.org/10.1038/s41590-025-02188-6","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy has been associated with acute neurotoxicity syndromes and with longer-term neurological symptoms. In Cell, Geraghty et al. identify the mechanism behind long-term cognitive symptoms after CAR T cell therapy. The authors used patient-derived xenograft mouse models of central nervous system (CNS) and non-CNS cancers, and an immunocompetent mouse model of a non-CNS cancer. They tested chronic effects on CNS immune state, oligodendroglial and myelin homeostasis, hippocampal neurogenesis, and cognitive function were tested after CAR T cell immunotherapy. CAR T cell therapy resulted in impaired cognition in the mice after clearing the tumor with CAR T cell therapy. They found increased levels of cytokines and chemokines in the cerebrospinal fluid, induced white matter microglial reactivity, disrupted oligodendroglial lineage cell dynamics, and impaired hippocampal neurogenesis. In a mouse model of acute lymphoblastic leukemia, microglial depletion rescued the cognitive deficits and inhibition of the receptor CCR3 rescued microglial dysregulation, oligodendrocyte loss and improved cognitive behavioral performance.Original reference: Cell https://doi.org/10.1016/j.cell.2025.03.041 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201586","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

Towards evidence-based immunology 循证免疫学

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-02 DOI: 10.1038/s41590-025-02180-0

David S. Khoury, Deborah Cromer, Bronwyn Bailey, Shanchita R. Khan, Deborah L. Burnett, Stephen J. Kent, Brian D. Rudd, Arnaud Marchant, Tari Turner, Miles P. Davenport

引用次数: 0

Astrocyte TRAIL promotes GBM 星形胶质细胞TRAIL促进GBM

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-02 DOI: 10.1038/s41590-025-02189-5

Laurie A. Dempsey

引用次数: 0

Regulatory T cell therapies to treat autoimmune diseases and transplant rejection 调节性T细胞疗法治疗自身免疫性疾病和移植排斥反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-06-02 DOI: 10.1038/s41590-025-02154-2

Jeffrey A. Bluestone, Bruce K. Burnett, Christine E. Crute, Mick D. Fellows, Megan Levings, Hervé Lebrec, Lucilia Pereira Mouriès, Jeffrey Rice, Patricia Rohan, Maria Grazia Roncarolo, Daniel Rotrosen

引用次数: 0