The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(7), P. 503 - 517

Published: Feb. 19, 2024

Language: Английский

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Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(2), P. 100473 - 100473

Published: Jan. 3, 2024

CD4+ T cells are key mediators of various autoimmune diseases; however, their role in disease progression remains unclear due to cellular heterogeneity. Here, we evaluated cell subpopulations using decomposition-based transcriptome characterization and canonical clustering strategies. This approach identified 12 independent gene programs governing whole heterogeneity, which can explain the ambiguity clustering. In addition, performed a meta-analysis public single-cell datasets over 1.8 million peripheral from 953 individuals by projecting onto reference cataloging frequency qualitative alterations populations 20 diseases. The analyses revealed that transcriptional were useful characterizing each predicting its clinical status. Moreover, genetic variants associated with diseases showed disease-specific enrichment within programs. results collectively provide landscape transcriptomes involved disease.

Language: Английский

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Distinct features of a peripheral T helper subset that drives the B cell response in dengue virus infection

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115366 - 115366

Published: March 1, 2025

Language: Английский

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Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Language: Английский

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Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis

European Respiratory Journal, Journal Year: 2024, Volume and Issue: 63(5), P. 2400386 - 2400386

Published: March 21, 2024

Introduction Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. Methods We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) 17 (Th17) cells, regulatory T-cells (Treg) interleukin (IL)-21 + CD4 in total or sorted peripheral blood mononuclear cells bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing was done exacerbated Antibodies T-/B-cell co-cultures vitro measured. Results had increased Th2 similar numbers Treg decreased circulating Th1 Th17 cells. IL-5 IL-13 IL-21 rarely detected controls, but significantly elevated the especially ones. found that mainly (Tph) (PD-1 CXCR5 − ), which also presented BALF patients. proportions Tph among while Transcriptome data showed Th2-skewed exhibited signatures follicular When co-cultured , induced differentiation autologous B-cells into plasmablasts enhanced production IgE. Conclusion identified a distinctly population IgE It may be biomarker therapeutic target for ABPA.

Language: Английский

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Single cell suppression profiling of human regulatory T cells

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Regulatory T cells (Treg) play an important role in regulating immune homeostasis health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide accurate picture of a physiologically relevant response. To overcome this limitation, we here develop 'single suppression profiling human Tregs' (scSPOT). scSPOT uses 52-marker CyTOF panel, division detection algorithm, whole PBMC system to assess the effect Tregs on all other types simultaneously. In head-to-head comparison, find having clearest effects effector memory CD8 through partial arrest, cycle inhibition, molecule downregulation. Additionally, identifies Treg phenotypic split previously observed viral infection propose modes action FDA-approved drugs Ipilimumab Tazemetostat. is thus scalable, robust, widely applicable, may be used better understand immunobiology screen for therapeutic compounds. Traditional regulatory (Tregs) assays utilize mixture population. Here authors (scSPOT) with

Language: Английский

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Expansion of HLA‐DR Positive Peripheral Helper T and Naive B Cells in Anticitrullinated Protein Antibody‐Positive Individuals At Risk for Rheumatoid Arthritis

Arthritis & Rheumatology, Journal Year: 2024, Volume and Issue: 76(7), P. 1023 - 1035

Published: Feb. 27, 2024

Objective To investigate immune dysregulation in the peripheral blood that contributes to pre‐rheumatoid arthritis (RA) stage of RA development anticitrullinated protein antibody (ACPA)+ individuals. Methods Using 37 markers by mass cytometry, we investigated mononuclear cells (PBMCs) from ACPA+ at‐risk individuals, early untreated patients with RA, and ACPA− controls Tokyo Women's Medical University cohort (n = 17 each group). Computational algorithms, FlowSOM Optimized t‐Distributed Stochastic Neighbor Embedding, were employed explore specific immunologic differences between study groups. These findings further evaluated, longitudinal changes explored, using flow cytometry PBMCs US‐based Targeting Immune Responses for Prevention included 11 individuals who later developed (pre‐RA), which 9 had post‐RA diagnosis (post‐RA), controls. Results HLA‐DR + helper T (Tph) cells, activated regulatory PD‐1 hi CD8 CXCR5 − CD11c CD38 naive B significantly expanded cohort. Expansion Tph was likewise found both pre‐RA time points Conclusion The expansion including those inflammatory classified supports a key role these transition RA. may identify new mechanistic target treatment prevention image

Language: Английский

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Peripheral helper T cells in human diseases

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 145, P. 103218 - 103218

Published: April 4, 2024

Peripheral helper T cells (Tph) are a specialized subset of CD4

Language: Английский

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SIRT3 Negatively Regulates TFH-Cell Differentiation in Cancer

Cancer Immunology Research, Journal Year: 2024, Volume and Issue: 12(7), P. 891 - 904

Published: April 17, 2024

Follicular helper T (TFH) cells are essential for inducing germinal center (GC) reactions to mediate humoral adaptive immunity in tumors; however, the mechanisms underlying TFH-cell differentiation remain unclear. In this study, we found that metabolism sensor sirtuin 3 (SIRT3) is critical and GC formation during tumor development viral infection. SIRT3 deficiency CD4+ intrinsically enhanced Mechanistically, damaged oxidative phosphorylation (OXPHOS) compensatively triggered NAD+-glycolysis pathway provide a cellular energy supply, which was necessary deficiency-induced differentiation. Blocking NAD+ synthesis-glycolysis signaling or recovering OXPHOS activities reversed induced by deficiency. Moreover, mTOR hypoxia-inducible factor 1α (HIF1α) axis be responsible HIF1α directly interacted with regulated activity of transcription Bcl6. Thus, our findings identify compensatory mechanism, mitochondrial SIRT3, triggers NAD+-dependent glycolysis injuries an mTOR-HIF1α-Bcl6 reprogram These data have implications future cancer immunotherapy research targeting cells.

Language: Английский

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Peripheral helper T cells, mavericks of peripheral immune responses

International Immunology, Journal Year: 2023, Volume and Issue: 36(1), P. 9 - 16

Published: Oct. 3, 2023

Peripheral helper T (Tph) cells have been established, through intensive efforts to elucidate local immune responses in human rheumatoid arthritis (RA), as a CD4 subset intimately involved acquired immunity peripheral tissues. Initially, Tph were noted population that produces high levels of CXCL13 RA synovial tissues, followed by demonstration their ability help B cells. In contrast follicular (Tfh) cells, do not express the transcription factor BCL6 but molecules such CXCL13, interleukin (IL)-21, and inducible T-cell costimulator (ICOS) Subsequent studies showed are associated with various diseases, including autoimmune infections, malignancies, development early life immunity. This review summarizes phenotype function discusses differentiation diversity conditions.

Language: Английский

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