Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 28, 2024

Tertiary lymphoid structures (TLSs) are defined as aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary (SLOs), the formation of TLSs relies on interaction between tissue inducer (LTi) cells and organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature TLSs, which may lead differences their functions. Growing evidence suggests that associated with various diseases, such cancers, autoimmune transplant rejection, chronic inflammation, infection, even ageing. However, detailed mechanisms behind these clinical associations not yet fully understood. The by TLS maturation localization affect immune function also unclear. Therefore, it necessary enhance understanding development at cellular molecular level, allow us utilize them improve microenvironment. In this review, we delve into composition, mechanism, potential therapeutic applications TLSs. Furthermore, discuss implications role markers response prognosis. Finally, summarize methods for detecting targeting Overall, provide comprehensive aim develop more effective strategies.

Language: Английский

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CAR Macrophages: a promising novel immunotherapy for solid tumors and beyond

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 23, 2024

Abstract With the advent of adoptive cellular therapy, chimeric antigen receptor (CAR)-T cell therapy has gained widespread application in cancer treatment and demonstrated significant efficacy against certain hematologic malignancies. However, due to limitations CAR-T treating solid tumors, other immune cells are being modified with CAR address this issue. Macrophages have emerged as a promising option, owing their extensive functions, which include presentation, powerful tumor phagocytosis, particularly active trafficking microenvironment. Leveraging unique advantages, CAR-macrophages (CAR-M) expected enhance effectiveness treatments novel form immunotherapy, potentially overcoming major challenges associated CAR-T/NK therapy. This review outlines primary mechanism underlying CAR-M recent progressions while also discussing further applications.

Language: Английский

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Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

Circulation Research, Journal Year: 2024, Volume and Issue: 134(12), P. 1681 - 1702

Published: June 6, 2024

Throughout our lifetime, each beat of the heart requires coordinated action multiple cardiac cell types. Understanding biology, its intricate microenvironments, and mechanisms that govern their function in health disease are crucial to designing novel therapeutical behavioral interventions. Recent advances single-cell spatial omics technologies have significantly propelled this understanding, offering insights into cellular diversity complex interactions tissue. This review provides a comprehensive overview landscape heart, bridging gap between suspension-based emerging situ approaches, focusing on experimental computational challenges, comparative analyses mouse human systems, rising contextualization cells within niches. As we explore at unprecedented resolution, integrating from both studies will pave way for diagnostic tools therapeutic interventions, ultimately improving outcomes patients with cardiovascular diseases.

Language: Английский

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CCL19⁺ Fibroblasts Promote Tertiary Lymphoid Structure in Oral Lichen Planus: A Retrospective Study

Oral Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

ABSTRACT Objectives The priming mechanism of adaptive immunity in oral mucositis remains unclarified. This study aimed to elucidate the mechanisms lichen planus (OLP), with a specific focus on role inducible tertiary lymphoid structures (iTLSs) and stromal‐immune microenvironments within OLP. Materials Methods We employed single‐cell RNA sequencing multiplex immunofluorescence staining characterize spatial characteristics transcriptional signature iTLSs To investigate whether presence influences disease severity OLP, we retrospectively collected clinical data from OLP patients. Results Based resolution analysis, identified distinct cellular compositions fibroblast‐immune cells interactions highlighted critical CCL19 + fibroblasts T‐cell chemotaxis, promoting development iTLSs. Lymphotoxin was demonstrated activate expressing CCL19. revealed significant correlation between increased marked by more atrophic‐erosive forms higher scores patients Conclusions present research proposed cell as essential factors OLP's inflammatory milieu, indicating structure local mucosa.

Language: Английский

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The Role of Chemokine (C‐C Motif) Ligand 7 (CCL7) in Hepatocellular Carcinoma: Expression, Function, and Mechanisms

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: March 1, 2025

AHepatocellular carcinoma (HCC) is a malignant neoplasm characterized by poor prognosis, with its incidence rising globally. Chemokine (C-C motif) ligand 7 (CCL7), chemokine protein, has been implicated in the progression of various cancers. Nonetheless, specific role CCL7 HCC yet to be elucidated. This study seeks examine expression and functional context HCC. Western blot immunohistochemistry were used detect tissues cell lines. Cell Counting Kit 8 (CCK8) assay, clonogenic transwell assay performed effects on SNU-878 cells. Immunofluorescence was analyze proteins associated epithelial interstitial transformation (EMT). activation PI3K/AKT pathway. In vivo tumorigenesis experiments assess tumorigenesis. The results showed that up-regulated tissues, exogenous promoted proliferation, migration, invasion, EMT cells VEGF secretion Furthermore, stimulated Further analysis revealed targeted CCR1 CCR2 enhance growth, metastasis CCR1/CCR2 silencing prevented from activating signaling pathway Moreover, facilitated vivo. Our findings indicate plays promoting growth tumorigenesis, potentially via targeting

Language: Английский

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Identification of novel IL17-related genes as prognostic and therapeutic biomarkers of psoriasis using comprehensive bioinformatics analysis and machine learning

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 2, 2025

Psoriasis is a common chronic skin disorder with polygenic background. It widely acknowledged that Th17/IL-17A axis plays key role in the pathogenesis of psoriasis. However, numerous regulatory genes upstream pathway remain undiscovered, creating knowledge gap our understanding genetic aspects axis. In this study, we employed machine learning algorithms to identify three target associated psoriasis: CCR7, IL2RG, and PLEK. The validation these was carried out specimens from psoriatic patients. vivo, investigations assessed relationship between IL-17A-related inflammation their connection phenotypes. To further confirm significance newly discovered gene, PLEK, performed experiments involving blockade its expression. Our bioinformatics analysis revealed novel closely linked These exhibited upregulated expression psoriasis, consistently aligning Inhibition PLEK reduced Th17/IL-17A-related alleviated show potential as biomarkers for being reported first time context. contribute by associating signaling pathway.

Language: Английский

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Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(9)

Published: Sept. 2, 2024

Abstract Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within lymph nodes mice afflicted with but this phenomenon was not observed in healthy mice. The specific distribution is driven by heightened expression CCL21-CCR7 axis facilitating targeted homing nodes. Within nodes, exhibit remarkable capacity modulate Th17 cell function, exerting pronounced anti-inflammatory effect. Transplanted stimulates secretion L-amino-acid oxidase (LAAO), response triggered elevated levels tumor necrosis factor-α (TNF-α) diseases through NF-κB pathway. presence LAAO indispensable efficacy MSC, it significantly contributes inhibition cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves potent suppressor activating aryl hydrocarbon receptor (AHR) These findings advance our understanding global immunomodulatory effects exerted providing valuable information optimizing outcomes.

Language: Английский

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Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Advanced NanoBiomed Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure function of lymphoid organs, while subsequent radiotherapy, chemotherapy, lymph node dissection further patient's immune system, leading to dysfunction, metabolic disorders, increased susceptibility infection, which seriously affect prognosis quality life. In this context, nanotechnology plays a key role in organ regeneration recovery, including improving therapeutic effect through targeted drug delivery systems, using imaging probes achieve tumor prediction early detection, combining nanoplatforms with immunotherapy photodynamic therapy synergistic effects, nanomaterials regulate microenvironment enhance sensitivity traditional treatments. addition, biophysical simulation strategies that simulate organs have also attracted widespread attention, aiming construct native cell environment support functional recovery damaged tissues, or cells lymphocytes induce specific responses. The multifaceted application provides promising prospects for repair.

Language: Английский

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Identification of Potential Ferroptosis Biomarkers and Analysis of Immune Cell Infiltration in Psoriasis Using Machine Learning

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2024, Volume and Issue: Volume 17, P. 1281 - 1295

Published: May 1, 2024

Background: Ferroptosis is a type of cell death characterized by the accumulation iron-dependent lethal lipid peroxides, which associated with various pathophysiological processes. Psoriasis chronic autoimmune skin disease accompanied abnormal immune infiltration and excessive production reactive oxygen species (ROS). Currently, its pathogenesis remains elusive, especially potential role ferroptosis in process. Methods: The microarrays GSE13355 (58 psoriatic specimens versus 122 healthy specimens) database were employed to identify common differentially expressed genes (DEGs) psoriasis ferroptosis. functions DEGs investigated through functional enrichment analysis protein-protein interaction analysis. diagnostic markers for among identified using four machine-learning algorithms. DGIdb was utilized explore therapeutic agents psoriasis. Additionally, CIBERSORT investigate Results: A total 8 identified, are involved intercellular signaling affect pathways response stress stimulation. Four algorithms poly (ADP-ribose) polymerase 12 (PARP12), frizzled homolog 7 (FZD7), arachidonate 15-lipoxygenase (ALOX15B) eight as 18 drugs targeting five candidates treating significant changes observed microenvironment patients Conclusion: This study has contributed our enhanced comprehension ferroptosis-related biomarkers diagnosis, well alterations Our findings offer valuable insights into diagnosis treatment Keywords: psoriasis, ferroptosis, biomarker,

Language: Английский

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Fish Collagen Peptides Enhance Thymopoietic Gene Expression, Cell Proliferation, Thymocyte Adherence, and Cytoprotection in Thymic Epithelial Cells via Activation of the Nuclear Factor-κB Pathway, Leading to Thymus Regeneration after Cyclophosphamide-Induced Injury

Marine Drugs, Journal Year: 2023, Volume and Issue: 21(10), P. 531 - 531

Published: Oct. 12, 2023

Prolonged thymic involution results in decreased thymopoiesis and output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is only means of generating fully mature T cells, identification strategies enhance regeneration crucial developing therapeutic interventions revert immune suppression immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities epithelial cells (TECs), including cell proliferation, thymocyte adhesion, gene expression thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTβ, IL-22R, RANK, LTβR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, CK8 through NF-κB signal transduction pathway. Furthermore, our also revealed cytoprotective effects FCPs on TECs against cyclophosphamide-induced cellular injury signaling Importantly, exhibited a significant capability facilitate mice after damage via Taken together, this sheds light role TEC function, thymopoiesis, regeneration, providing greater insight into development novel for effective thymus repopulation numerous clinical conditions which reconstitution required.

Language: Английский

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