Treg–tissue cell interactions in repair and regeneration

The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(6)

Опубликована: Апрель 26, 2024

Regulatory T (Treg) cells are classically known for their critical immunosuppressive functions that support peripheral tolerance. More recent work has demonstrated Treg produce pro-repair mediators independent of function, a process is to repair and regeneration in response numerous tissue insults. These factors act on resident parenchymal structural initiate tissue-specific context. This review examines interactions between tissue-resident non-immune cells—in the context repair, fibrosis, cancer—and discusses areas future exploration.

Язык: Английский

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Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage

Immunity, Год журнала: 2025, Номер 58(2), С. 397 - 411.e6

Опубликована: Янв. 31, 2025

Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections cancers. Here, we examined the role of regulatory (Treg) cells on thymic regeneration. Treg frequencies increased in thymus various acute models. Depletion impaired regeneration, impacting both thymocyte compartment stromal compartment; adoptive transfer enhanced Expansion circulating cells, as opposed that tissue resident recent emigrants, explained this increase, seen using parabiotic Single-cell analyses recirculating revealed expression regenerative factors, including cytokine amphiregulin. Deletion amphiregulin these regeneration injured thymus. We identified an analogous population CD39+ICOS+ human Our findings point potential therapeutic avenues address aging- treatment-induced immunosuppression.

Язык: Английский

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Immunometabolism of Tregs: mechanisms, adaptability, and therapeutic implications in diseases

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 23, 2025

Immunometabolism is an emerging field that explores the intricate interplay between immune cells and metabolism. Regulatory T (Tregs), which maintain homeostasis in immunometabolism, play crucial regulatory roles. The activation, differentiation, function of Tregs are influenced by various metabolic pathways, such as Mammalian targets rapamycin (mTOR) pathway glycolysis. Correspondingly, activated can reciprocally impact these pathways. also possess robust adaptive capabilities, thus enabling them to adapt microenvironments, including tumor microenvironment (TME). complex mechanisms diseases intriguing, particularly conditions like MASLD, where significantly upregulated contribute fibrosis, while diabetes, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), they show downregulation reduced anti-inflammatory capacity. These phenomena suggest differentiation environment, imbalances either lead development diseases. Thus, moderate inhibitory capacity critical for maintaining system balance. Given unique immunoregulatory abilities Tregs, targeted therapeutic drugs may position novel immunotherapy. This could restoring balance, resolving dysregulation, fostering innovation progress

Язык: Английский

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Treg derived Amphiregulin protects from murine lupus nephritis via tissue reparative effects

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 5, 2025

Systemic lupus erythematosus (SLE) is a common autoimmune disease that affects multiple organ systems. Among the most severe manifestations of SLE nephritis (LN), which causes particularly high morbidity. Recently, we identified amphiregulin (AREG), an epidermal growth factor receptor ligand, as key mediator LN via downregulation pathogenic CD4+ T-cell responses. In human LN, AREG mainly produced by regulatory T cells (Tregs) and monocytes/macrophages (M/M). Since AREG´s functions have been shown to vary considerably depending on source, aimed clarify cell-type-specific roles using pristane model LN. Conditional knockout mice lacking Treg- but not M/M-derived showed worse outcome at 12 15 months with increased glomerular cell proliferation, apoptosis renal tissue fibrosis. Interestingly, immune responses were relevantly affected lack from either leukocyte indicating different mechanism. this respect, in vitro studies demonstrated improved wound healing murine mesangium tubulus enhanced regeneration sprouting endothelial after incubation recombinant AREG. These findings underscore importance Treg-derived protection fibrosis highlighting potential therapeutic target.

Язык: Английский

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The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 6, 2025

Tissue resident regulatory T cells (tissue Tregs) are vital for maintaining immune homeostasis and controlling inflammation. They aid in repairing damaged tissues influencing the progression of fibrosis. However, despite extensive research on how tissue Tregs interact with non-immune during repair, their pro- anti-fibrotic effects chronic injury remain unclear. Understanding various cell types, as well roles fibrosis, is crucial uncovering mechanisms behind these conditions. In this review, we describe repair fibrosis across different explore potential strategies regulating homeostasis. These insights hold promise providing new perspectives approaches treatment irreversible fibrotic diseases.

Язык: Английский

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Lapatinib ameliorates skin fibrosis by inhibiting TGF-β1/Smad and non-Smad signaling pathway

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 11, 2025

Skin fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) in the dermis, can lead to hypertrophic scars and impaired mobility. The ErbB family receptor tyrosine kinases, including ErbB1 ErbB2, plays a crucial role organ but their specific impact on skin fibrosis is less understood. This study investigated ErbB2 therapeutic potential lapatinib, dual kinase inhibitor. Using qPCR, cell culture assays, Western blotting, vivo models, we found significant upregulation keloid tissues fibroblasts. Lapatinib treatment resulted dose-dependent decrease expression, which suppressed expression fibroblast activation markers. Our findings suggest that lapatinib may be promising agent for targeting ErbB1/ErbB2 modulating TGF-β1/Smad2/3/Erk/Akt signalling pathways. These results warrant further clinical investigation into treating related conditions.

Язык: Английский

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Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment

Food Research International, Год журнала: 2025, Номер unknown, С. 116207 - 116207

Опубликована: Март 1, 2025

Язык: Английский

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Role of regulatory T cells in inflammatory liver diseases

Autoimmunity Reviews, Год журнала: 2025, Номер unknown, С. 103806 - 103806

Опубликована: Март 1, 2025

Язык: Английский

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Investigation of the Pathogenesis of Liver Fibrosis Associated with Type 2 Diabetes Mellitus via Bioinformatic Analysis

Biomedicines, Год журнала: 2025, Номер 13(4), С. 840 - 840

Опубликована: Апрель 1, 2025

Background: The global prevalence of type 2 diabetes mellitus (T2DM) with liver fibrosis is rising, T2DM identified as an independent risk factor and key prognostic for fibrosis. However, the underlying mechanisms remain unclear. Methods: To explore shared pathogenesis T2DM, we analyzed gene expression profiles from GEO database. co-differentially expressed genes (co-DEGs) were subsequently through functional enrichment, protein–protein interaction (PPI) network construction, transcription prediction, drug prediction. Machine learning algorithms then applied to identify genes. Results: A total 175 co-DEGs identified. Functional enrichment analysis indicated their involvement in extracellular matrix (ECM) remodeling, inflammation, PI3K/Akt signaling pathway. Through PPI four algorithms, eight hub identified, including SPARC, COL4A2, THBS1, LUM, TIMP3, COL3A1, IGFBP7, FSTL1, THBS1 being recognized a by machine learning. upregulation was observed both diseases, it closely related progression T2DM. Transcription detected 29 regulators these Drug prediction suggested that retinoic acid may serve potential therapeutic agent. Conclusions: This study provides novel insights into offer targets clinical intervention.

Язык: Английский

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Antifibrotic Therapies for Metabolic Dysfunction-associated Steatotic Liver Disease

JHEP Reports, Год журнала: 2025, Номер unknown, С. 101421 - 101421

Опубликована: Апрель 1, 2025

Язык: Английский

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