A Distinctive γδ T Cell Repertoire in NOD Mice Weakens Immune Regulation and Favors Diabetic Disease

O’Brien, Rebecca L.; Matsuda, Jennifer L.; Aydintug, M. Kemal; Jin, Niyun; Phalke, Swati; Born, Willi K.

doi:10.3390/biom12101406

Cited by 5 publications

(2 citation statements)

References 89 publications

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“…Although we showed an increased frequency of γδ T cells in diabetic corneas, little is known about their roles in diabetic corneal pathological alterations. The exact roles of γδ T cells in the development of diabetes remain complex, depending on different γδ T cell subsets ( 46 , 47 ). Therefore, to comprehend the functions of γδT cells in diabetic corneal diseases, the functional properties of γδT cells under diabetic conditions should be fully determined in future investigations.…”

Section: Discussionmentioning

confidence: 99%

Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice

Qin,

Li,

Wang

et al. 2023

Front. Endocrinol.

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IntroductionDiabetic ocular complications include sight-threatening consequences and decreased corneal sensitivity, characterized by decreased tear production, corneal sensitivity and delayed corneal epithelial wound healing. The pathogenesis of diabetic corneal disorders remains largely unknown. Growing evidence implies the participation of immune cells in the development of diabetic corneal diseases. Nonetheless, the immunological changes that result in diabetic corneal problems are largely unknown.MethodsMass cytometry by time of flight (CyTOF) was used to investigate immune cell cluster alterations associated with diabetic corneal disorders. CyTOF test was performed on corneal cells at a single level from 21-week-old diabetic (db/db) and non-diabetic (db/m) mice. A panel of 41 immune-related markers monitored different immune cell types in diabetic corneas. To investigate the proportion of each immune cell subpopulation, an unsupervised clustering method was employed, and T-distributed stochastic neighbor embedding was used to visualize the distinctions between different immune cell subsets.ResultsThrough CyTOF test, we identified 10 immune cell subsets in the corneal tissues. In a novel way, we discovered significant immune alterations in diabetic corneas, including pronounced alterations in T cells and myeloid cell subgroups in diabetic corneas linked to potential biomarkers, including CD103, CCR2, SiglecF, Ly6G, and CD172a. Comprehensive immunological profiling indicated remarkable changes in the immune microenvironment in diabetic corneas, characterized by a notable decrease in CD103+CD8+ tissue-resident memory T (TRM) cells and Tregs, as well as a dramatic increase of γδT cells and subsets of CD11b+Ly6G+ myeloid-derived suppressor cells (MDSCs).ConclusionCyTOF analysis revealed significant alterations in the immune microenvironment during the development of diabetic corneal complications. This study mapped the immune microenvironment landscape of type 2 diabetic corneas, providing a fundamental understanding of immune-driven diabetic corneal disorders.

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Section: Discussionmentioning

confidence: 99%

Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice

Qin,

Li,

Wang

et al. 2023

Front. Endocrinol.

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“…524 Moreover, a recent study illuminated the dualistic, both protective and pathogenic, role that γδ T cells enact in T1D contingent upon their functional subsets. 525 As such, the precise role of γδ T cells in diabetes remains to be clarified and may pivot on specific contextual factors. Additionally, the involvement of γδ T cells in type 2 diabetes (T2D) 526,527 remains relatively unexplored, with a scarcity of available literature to facilitate in-depth discussions.…”

Section: γδ T Cells In Psoriasismentioning

confidence: 99%

γδ T cells: origin and fate, subsets, diseases and immunotherapy

Hu,

et al. 2023

Sig Transduct Target Ther

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The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2+ γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.

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Intestinal mucosal immunity and type 1 diabetes: Non‐negligible communication between gut and pancreas

Liu,

Zhang,

Chen

et al. 2024

Diabetes Obesity Metabolism

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Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell‐mediated pancreatic β cell loss, resulting in lifelong absolute insulin deficiency and hyperglycaemia. Environmental factors are recognized as a key contributor to the development of T1D, with the gut serving as a primary interface for environmental stimuli. Recent studies have revealed that the alterations in the intestinal microenvironment profoundly affect host immune responses, contributing to the aetiology and pathogenesis of T1D. However, the dominant intestinal immune cells and the underlying mechanisms remain incompletely elucidated. In this review, we provide an overview of the possible mechanisms of the intestinal mucosal system that underpin the pathogenesis of T1D, shedding light on the roles of both non‐classical and classical immune cells in T1D. Our goal is to gain insights into how modulating these immune components may hold potential implications for T1D prevention and provide novel perspectives for immune‐mediated therapy.

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A Distinctive γδ T Cell Repertoire in NOD Mice Weakens Immune Regulation and Favors Diabetic Disease

Cited by 5 publications

References 89 publications

Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice

Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice

γδ T cells: origin and fate, subsets, diseases and immunotherapy

Intestinal mucosal immunity and type 1 diabetes: Non‐negligible communication between gut and pancreas

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