The role of interferon signaling in neurodegeneration and neuropsychiatric disorders DOI Creative Commons
Daniel W. Sirkis, Alexis P. Oddi, Caroline Jonson

и другие.

Frontiers in Psychiatry, Год журнала: 2024, Номер 15

Опубликована: Окт. 3, 2024

Recent advances in transcriptomics research have uncovered heightened interferon (IFN) responses neurodegenerative diseases including Alzheimer's disease, primary tauopathy, Parkinson's TDP-43 proteinopathy, and related mouse models. Augmented IFN signaling is now relatively well established for microglia these contexts, but emerging work has highlighted a novel role IFN-responsive T cells the brain peripheral blood some types of neurodegeneration. These findings complement body literature implicating dysregulated neuropsychiatric disorders major depression post-traumatic stress disorder. In this review, we will characterize integrate our understanding discuss how sex ancestry modulate response, examine potential mechanistic explanations upregulation antiviral-like pathways seemingly non-viral neurological psychiatric disorders.

Язык: Английский

Neoself-antigens are the primary target for autoreactive T cells in human lupus DOI
Shunsuke Mori,

Masako Kohyama,

Yoshiaki Yasumizu

и другие.

Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

10
Single-cell analysis in rheumatic and allergic diseases: insights for clinical practice DOI
Masayuki Nishide, Hiroshi Shimagami, Atsushi Kumanogoh

и другие.

Nature reviews. Immunology, Год журнала: 2024, Номер 24(11), С. 781 - 797

Опубликована: Июнь 24, 2024

Язык: Английский

Процитировано

7
Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults DOI Creative Commons
Qiuyu Gong, Mehul Sharma, Emma L. Kuan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 14, 2024

The generation and maintenance of protective immunity is a dynamic interplay between host environment that impacted by age. Understanding fundamental changes in the healthy immune system occur over lifespan critical developing interventions for age-related susceptibility to infections diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) examined human peripheral 300 adults, with 96 young older adults followed two years yearly vaccination. resulting resource includes scRNA-seq datasets >16 million PBMCs, interrogating 71 cell subsets from our new Immune Health Atlas. This study allows unique insights into composition transcriptional state cells at homeostasis, vaccine perturbation, across We find T specifically accumulate more than other cells, independent inflammation chronic perturbation. Moreover, impaired memory B responses vaccination are linked Th2-like shift adults' CD4 revealing possible mechanisms dysregulation during aging. extensive provided suite exploration tools https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ enhance data accessibility further understanding health

Язык: Английский

Процитировано

6
Reproducible single cell annotation of programs underlying T-cell subsets, activation states, and functions DOI Creative Commons
Dylan Kotliar, Michelle Curtis,

Ryan Agnew

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 5, 2024

Abstract T-cells recognize antigens and induce specialized gene expression programs (GEPs) enabling functions including proliferation, cytotoxicity, cytokine production. Traditionally, different classes of helper express mutually exclusive responses – for example, Th1, Th2, Th17 programs. However, new single-cell RNA sequencing (scRNA-Seq) experiments have revealed a continuum T-cell states without discrete clusters corresponding to these subsets, implying the need analytical frameworks. Here, we advance characterization with T-CellAnnoTator (TCAT), pipeline that simultaneously quantifies pre-defined GEPs capturing activation cellular subsets. From 1,700,000 from 700 individuals across 38 tissues five diverse disease contexts, discover 46 reproducible reflecting known core exhaustion, T effector states. We experimentally characterize several novel apply TCAT describe exhaustion in Covid-19 cancer, providing insight into function diseases.

Язык: Английский

Процитировано

4
Analysis of effector/memory regulatory T cells from arrhythmogenic cardiomyopathy patients identified IL-32 as a novel player in ACM pathogenesis DOI Creative Commons

Salwa Soussi,

Angela Serena Maione, Lise Lefèvre

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 11, 2025

Abstract Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disorder that causes sudden death and progressive heart failure. Besides fibro-fatty replacement myocyte degenerative changes, inflammatory patchy infiltrates are found in myocardial histological analysis of ACM patients. Inflammatory cells could actively participate pathogenesis, contributing to the alteration microenvironment homeostasis, thus triggering disease evolution. In order characterize immune-derived mediators involved peripheral blood mononuclear from patients were characterized compared healthy controls’ ones. Flow cytometry revealed a lower frequency CD4 + T helper type 1 cells, NK terminally differentiated CD8 EMRA age-matched controls. contrast, higher proportion effector/memory FOXP3 CCR4 CD45RO regulatory (Treg) Single-cell RNA-seq performed on isolated memory Treg (mTreg) controls identified 6 clusters by specific gene signatures related tissue repair immunosuppressive pathways. Notably, interleukin 32 (IL-32) was most differentially expressed mTreg with respect Treatment human mesenchymal stromal recombinant IL-32 vitro promoted lipid droplet accumulation collagen deposition, identifying as new potential player immune-mediated trigger ACM. Overall, we here provide first complete characterization circulating immune revealing abundance Treg. The high expression may contribute accelerated remodeling patients’ hearts.

Язык: Английский

Процитировано

0
Emerging Mechanisms and Biomarkers Associated with T-Cells and B-Cells in Autoimmune Disorders DOI
Azhagu Madhavan Sivalingam

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Фев. 11, 2025

Язык: Английский

Процитировано

0
Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder DOI Creative Commons

Tomohiro Yata,

Go Sato, Kotaro Ogawa

и другие.

Cell Genomics, Год журнала: 2025, Номер unknown, С. 100776 - 100776

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Single-cell multi-omics profiling uncovers the immune heterogeneity in HIV-infected immunological non-responders DOI
Xiaosheng Liu,

Leidan Zhang,

Xiaodi Li

и другие.

EBioMedicine, Год журнала: 2025, Номер 115, С. 105667 - 105667

Опубликована: Апрель 6, 2025

Язык: Английский

Процитировано

0
Single-cell meta-analysis of T cells reveals clonal dynamics of response to checkpoint immunotherapy DOI Creative Commons
Ofir Shorer,

Asaf Pinhasi,

Keren Yizhak

и другие.

Cell Genomics, Год журнала: 2025, Номер unknown, С. 100842 - 100842

Опубликована: Апрель 1, 2025

Despite the crucial role of T cell clones in anti-tumor activity, their characterization and association with clinical outcomes following immune checkpoint inhibitors are lacking. Here, we analyzed paired single-cell RNA sequencing/T receptor sequencing 767,606 cells across 460 samples spanning 6 cancer types. We found a robust signature response based on expanded CD8+ that differentiates responders from non-responders. Analysis persistent showed transcriptional changes differentially induced by therapy different groups, suggesting an improved reinvigoration capacity responding patients. Moreover, gene trajectory analysis revealed pseudo-temporal state de novo associated outcomes. Lastly, shared between tumor blood more abundant non-responders execute distinct programs. Overall, our results highlight differences clonal states linked to patient response, offering valuable insights into mechanisms driving effective immunity.

Язык: Английский

Процитировано

0
Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression DOI Creative Commons
Akikazu Harada, Yoshiaki Yasumizu,

Takeshi Harada

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 17, 2025

Wnt5a, a representative Wnt ligand that activates the β-catenin-independent pathway, has been shown to promote tumorigenesis. However, it is unclear where Wnt5a produced and how affects colon cancer aggressiveness. In this study, we demonstrate expressed in fibroblasts near luminal side of tumor, its depletion suppresses mouse formation. To characterize specific fibroblast subtype, meta-analysis human single-cell RNA-seq data performed. The results show hypoxia-induced inflammatory (InfFib), accompanied by activation HIF2. Moreover, maintains InfFib through suppression angiogenesis mediated soluble VEGF receptor1 (Flt1) secretion from endothelial cells, thereby inducing further hypoxia. also produces epiregulin, which promotes growth. Here, acts on hypoxic environment InfFib, contributing progression InfFib.

Язык: Английский

Процитировано

0