scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in T
            <sub>reg</sub>
            function

Gellatly, Kyle; Strassner, James P.; Essien, Kingsley I.; Refat, Maggi Ahmed; Murphy, Rachel L.; Coffin-Schmitt, A.; Pandya, Amit G.; Tovar‐Garza, Andrea; Frisoli, Michael L.; Fan, Xueli; Ding, Xiaolan; Kim, E.; Abbas, Zainab; McDonel, Patrick; Garber, Manuel; Harris, John E.

doi:10.1126/scitranslmed.abd8995

Cited by 67 publications

(66 citation statements)

References 72 publications

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“…To better understand the initiation and progression of vitiligo, Gellatly et al employed suction blistering and scRNA‐seq on affected and unaffected skin in vitiligo patients along with healthy individuals’ skin 66 …”

Section: Applications In Skin Researchmentioning

confidence: 99%

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Theocharidis

Tekkela

Veves

et al. 2022

Experimental Dermatology

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The human skin is defined by a multilayer architecture based on diverse cell populations of mainly keratinocytes and fibroblasts, as well as various immune cells, melanocytes, adipocytes and endothelial cells that orchestrate events leading to wound repair of pathogenic infections and exposure to ultraviolet radiation and toxic compounds. 1 The transcriptomic profile of skin can provide information on gene expression, non-coding regulatory elements and gene splicing, and therefore shed light on skin physiology and pathology. Earlier approaches such as bulk RNA-seq and microarrays provided information about the average transcriptome status

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Section: Applications In Skin Researchmentioning

confidence: 99%

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Theocharidis

Tekkela

Veves

et al. 2022

Experimental Dermatology

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“…For example, ligand–receptor analysis revealed the regulatory potential from resident epidermal/mesenchymal cells to dendritic cells during psoriasis [ 59 ]. More recently, cell–cell communication analysis of scRNA-seq of human vitiligo revealed that cell type–specific signaling programs and CCR5–CCL5 signaling was critical to effector CD8+ T cell and Treg function in vitiligo, implying the potential role of chemokine circuits in driving lymphocyte localization [ 60 ].…”

Section: Biological Insights Gained By Cell–cell Communication Analys...mentioning

confidence: 99%

Computational exploration of cellular communication in skin from emerging single-cell and spatial transcriptomic data

Jin

Ramos

2022

Biochemical Society Transactions

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Tissue development and homeostasis require coordinated cell–cell communication. Recent advances in single-cell sequencing technologies have emerged as a revolutionary method to reveal cellular heterogeneity with unprecedented resolution. This offers a great opportunity to explore cell–cell communication in tissues systematically and comprehensively, and to further identify signaling mechanisms driving cell fate decisions and shaping tissue phenotypes. Using gene expression information from single-cell transcriptomics, several computational tools have been developed for inferring cell–cell communication, greatly facilitating analysis and interpretation. However, in single-cell transcriptomics, spatial information of cells is inherently lost. Given that most cell signaling events occur within a limited distance in tissues, incorporating spatial information into cell–cell communication analysis is critical for understanding tissue organization and function. Spatial transcriptomics provides spatial location of cell subsets along with their gene expression, leading to new directions for leveraging spatial information to develop computational approaches for cell–cell communication inference and analysis. These computational approaches have been successfully applied to uncover previously unrecognized mechanisms of intercellular communication within various contexts and across organ systems, including the skin, a formidable model to study mechanisms of cell–cell communication due to the complex interactions between the different cell populations that comprise it. Here, we review emergent cell–cell communication inference tools using single-cell transcriptomics and spatial transcriptomics, and highlight the biological insights gained by applying these computational tools to exploring cellular communication in skin development, homeostasis, disease and aging, as well as discuss future potential research avenues.

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“…The expression of immune profile including transcription factor T-beta, TBX21 (T-Box Transcription Factor 21), CXCR3, and CCR5 (C-C Motif Chemokine Receptor 5) in T reg is believed to support the formation of resident memory T cells ( Ferreira et al, 2020 ). Current studies based on single-cell RNA sequencing of human vitiligo reveals that CCL5-CCR5 cytokine signaling serve as a chemokine circuit between effector CD8 + T cells and T reg cells ( Gellatly et al, 2021 ). Therefore, modulating the immune response is considered as a therapeutic target for the treatment of vitiligo.…”

Section: Pathogenesis Of Immunity In Vitiligomentioning

confidence: 99%

Vitiligo: An Autoimmune Skin Disease and its Immunomodulatory Therapeutic Intervention

Chang

Lee

Kuo

et al. 2021

Front. Cell Dev. Biol.

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Vitiligo is a chronic autoimmune depigmenting skin disorder characterized by patches of the skin losing functional melanocytes. Multiple combinatorial factors are involved in disease development, among which immune T cells play a prominent role. The immune cells implicated in melanocyte destruction through adaptive immunity include CD8+ cytotoxic T cells and regulatory T cells, and aberrantly activated skin-resident memory T cells also play a role in melanocyte destruction. Over the past several years, major progress in understanding vitiligo pathogenesis has led to the development of targeted therapies. Janus kinase (JAK) inhibitors, which share the similar mechanism that autoactivates CD8+ T cells in chronic inflammatory diseases, have been reported to have therapeutic significance in vitiligo. Recently, immunomodulatory therapeutic interventions in vitiligo have been emerging. Mesenchymal stem cells (MSCs) regulate cytokine secretion and the balance of T-cell subsets, which makes them a promising cell-based treatment option for autoimmune diseases. The induction of MSC-mediated immunomodulation is complicated and occurs by contact-dependent mechanisms and soluble extracellular vesicle (EV) mediators. EVs released from MSCs contain various growth factors and cytokines with anti-inflammatory effects in the skin immune response. Here, we summarize and discuss the progress to date in targeted therapies that immunomodulate the niche environment of vitiligo, from the clinical trial of JAK inhibitors to the potential of MSCs and MSC-EVs. The available information was collected to highlight the need for further research into the treatment of vitiligo.

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scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in T _reg function

Abstract: scRNA-seq of human vitiligo samples reveals complex autoimmune networks, including a role for CCR5 in T reg function.

Cited by 67 publications

References 72 publications

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Computational exploration of cellular communication in skin from emerging single-cell and spatial transcriptomic data

Vitiligo: An Autoimmune Skin Disease and its Immunomodulatory Therapeutic Intervention

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scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in T reg function

Abstract: scRNA-seq of human vitiligo samples reveals complex autoimmune networks, including a role for CCR5 in T reg function.

Cited by 67 publications

References 72 publications

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Single‐cell transcriptomics in human skin research: available technologies, technical considerations and disease applications

Computational exploration of cellular communication in skin from emerging single-cell and spatial transcriptomic data

Vitiligo: An Autoimmune Skin Disease and its Immunomodulatory Therapeutic Intervention

Contact Info

Product

Resources

About

scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in T _reg function