Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting

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

Опубликована: Янв. 29, 2025

Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against self-antigens, but how these autoreactive cells relate to tissue pathology remains unclear. Here we perform single-cell transcriptomic and receptor analyses of circulating, self-antigen-specific from patients with AILD identify a subset liver-autoreactive distinct B-helper transcriptional profile characterized by PD-1, TIGIT HLA-DR expression. These share clonal relationships expanded intrahepatic exhibit signatures overlapping tissue-resident in chronically inflamed environments. Using mouse model, demonstrate that, following antigen recognition the liver, acquire an exhausted phenotype, play crucial role damage, are controlled immune checkpoint pathways. Our findings thus suggest that circulating imprinted chronic exposure promote inflammation, thereby serving as potential target for developing biomarkers therapies AILD.

Язык: Английский

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Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes

The Journal of Immunology, Год журнала: 2025, Номер 214(1), С. 12 - 22

Опубликована: Янв. 1, 2025

The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. most promising biomarkers of response were late expansion exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 cells, neither which can be used to measure responses the weeks after treatment. Thus, we investigated whether early changes immunophenotypes could serve as activity. We characterized by flow cytometry identified an exhausted-like population CD2low effector memory coexpressing TIGIT PD1 that expanded 11 wk start This was not entirely spared from alefacept-mediated depletion vivo or vitro but recovered through homeostatic proliferation vivo. Proliferation TIGIT+PD1+ increased with treatment, a concomitant reduction proinflammatory cytokine production. persistent increase specific treatment; 2 other depleting therapies, teplizumab anti-thymocyte globulin, induced only transient this population. Our data suggest expanding represents biomarker treatment effects alefacept. nondepleting on production also agonistic activity CD2 targeted therapy.

Язык: Английский

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Emerging Mechanisms and Biomarkers Associated with T-Cells and B-Cells in Autoimmune Disorders

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

Опубликована: Фев. 11, 2025

Язык: Английский

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Role of CD4+ T cells in cancer immunity: a single-cell sequencing exploration of tumor microenvironment

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 14, 2025

Recent oncological research has intensely focused on the tumor immune microenvironment (TME), particularly functions of CD4 + T lymphocytes. CD4+ lymphocytes have been implicated in antigen presentation, cytokine release, and cytotoxicity, suggesting their contribution to dynamics TME. Furthermore, application single-cell sequencing yielded profound insights into phenotypic diversity functional specificity cells In this review, we discuss current findings from analyses, emphasizing heterogeneity cell subsets implications immunology. addition, review critical signaling pathways molecular networks underpinning activities, thereby offering novel perspectives therapeutic targets strategies for cancer treatment prognosis.

Язык: Английский

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Frequency of dengue virus–specific T cells is related to infection outcome in endemic settings

JCI Insight, Год журнала: 2025, Номер 10(4)

Опубликована: Фев. 23, 2025

Dengue is widespread in tropical and subtropical regions globally imposes a considerable disease burden. Annually, dengue virus (DENV) causes up to 400 million infections, of which approximately 25% present with clinical manifestations ranging from mild fatal. Despite its significance as growing public health concern, developing effective DENV vaccines has been challenging. One reason the lack comprehensive understanding influence exerted by prior infections immune responses cross-reactive properties. To investigate this, we collected samples pediatric cohort study dengue-endemic Managua, Nicaragua. We characterized T cell 71 healthy children who had previously experienced 1 or more natural who, within year after sample collection, subsequent infection that was either symptomatic inapparent. Our investigated effect preexisting DENV-specific on outcomes infection. assessed using an activation-induced marker assay. Children only displayed heterogeneous CD4+ CD8+ frequencies. In contrast, 2 showed significantly higher frequencies associated inapparent rather than These findings demonstrate protective role cells against advance efforts identify correlates dengue.

Язык: Английский

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Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Insights into pathogenesis and biomarkers of prognosis

Seminars in Immunology, Год журнала: 2025, Номер 78, С. 101944 - 101944

Опубликована: Март 14, 2025

Язык: Английский

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Pemphigoid disease model systems for clinical translation

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Pemphigoid diseases constitute a group of organ-specific autoimmune characterized and caused by autoantibodies targeting autoantigens expressed in the skin mucous membranes. Current therapeutic options are still based on unspecific immunosuppression that is associated with severe adverse events. Biologics, IL4-pathway or IgE expected to change treatment landscape pemphigoid diseases. However, clinical studies demonstrated these pathways alone most likely not sufficient meet patient healthcare partitioners expectations. Hence, model systems needed identify validate novel targets These include pre-clinical animal models, vitro ex vivo systems, hypothesis-driven drug repurposing, as well exploitation real-world-data. In this review, we will highlight medical need for diseases, in-depth discuss advantages disadvantages available disease systems. Ultimately, how rapid translation can be achieved benefit patients.

Язык: Английский

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The immunological processes behind aquaporin 4-antibody seropositive neuromyelitis optica spectrum disorders

Seminars in Immunology, Год журнала: 2025, Номер 78, С. 101945 - 101945

Опубликована: Март 29, 2025

Ever since the discovery of pathogenic aquaporin 4-specific antibodies in serum patients with neuromyelitis optica spectrum disorders current knowledge about clinical observations and diagnosis, underlying pathology resulting therapies have been put forward excellent reviews primary publications. However, order to further develop novel strategies for treatment this disease, there is an urgent need understand immunological processes associated formation antibodies, aberrant immune responses observed affected patients. In review, we will highlight evaluate important studies on these processes.

Язык: Английский

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Tolerance After Hematopoietic Stem Cell Transplantation

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology

The Journal of Cardiovascular Aging, Год журнала: 2025, Номер 5(2)

Опубликована: Апрель 22, 2025

Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, is driven by molecular cellular mechanisms described in hallmarks aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator fibrinolysis, also mediates processes like stiffness, senescence, immune evasion. This review highlights PAI-1’s role cardiovascular with special emphasis on hallmark It further explores therapeutic potential, focus its contribution to ECM remodeling, senescence signaling, checkpoint regulation. Targeting PAI-1 could provide promising strategy mitigate disease.

Язык: Английский

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