Regulatory T Cells Require CCR6 for Skin Migration and Local Suppression of Vitiligo

Essien, Kingsley I.; Katz, Erica L.; Strassner, James P.; Harris, John E.

doi:10.1016/j.jid.2022.05.1090

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…Later, it was demonstrated that CXCR3 plays a role in T cell migration into the inflamed skin [57]. More recently, CCR6 was shown to mediate Treg migration into the skin of vitiligo patients [58]. The percentage of Th1 in SSc PB was found to be decreased [59][60][61] or unchanged [62] and accompanied by a bias toward Th2 polarization [1,61,62], but Th1 cells from SSc patients present an activated phenotype [63], indicating that they play an active role in SSc.…”

Section: Discussionmentioning

confidence: 99%

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients

Laranjeira

Santos²,

Salvador

et al. 2023

Biomedicines

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Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, n = 6) and SSc patients (n = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4+, CD8+, CD4+CD8+, CD4-CD8-, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc’s pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system’s malfunction.

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Section: Discussionmentioning

confidence: 99%

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients

Laranjeira

Santos²,

Salvador

et al. 2023

Biomedicines

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“…Because of their significant involvement in various pathologies, chemokines and their receptors have been the focus of therapeutic discovery for clinical investigations in vitiligo. Several studies demonstrate reduced levels of CCL5/CCR4, CCL22, CCL21, and CCR6 in vitiligo skin, which could explain the failure of circulating Tregs to localize to the skin [ 126 , 129 , 134 , 135 , 136 , 137 ], thus suggesting that the modulating expression of these chemokines may be potential therapeutic targets in vitiligo. Therefore, it is envisaged that after modulation, these chemokines may re-establish proper immune regulation and self-tolerance by increasing the frequency of Treg migration and skin homing into vitiligo lesions [ 116 , 136 ].…”

Section: Role Of Tregs In Select Autoimmune Skin Diseasesmentioning

confidence: 99%

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers

Oparaugo

Ouyang

Nguyen

et al. 2023

IJMS

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Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the immune system is activated. Several studies have documented the critical role of Tregs in suppressing the functions of effector T cells and antigen-presenting cells. Under certain conditions, Tregs can lose their suppressive capability, leading to a compromised immune system. For example, mutations in the Treg transcription factor, Forkhead box P3 (FOXP3), can drive the development of autoimmune diseases in multiple organs within the body. Furthermore, mutations leading to a reduction in the numbers of Tregs or a change in their function facilitate autoimmunity, whereas an overabundance can inhibit anti-tumor and anti-pathogen immunity. This review discusses the characteristics of Tregs and their mechanism of action in select autoimmune skin diseases, transplantation, and skin cancer. We also examine the potential of Tregs-based cellular therapies in autoimmunity.

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“…Furthermore, memory T cells are thought to remain and contribute to the recurrence of the lesions [4]. Recent data suggest regulatory T cells might play a role in promoting the immune response in vitiligo [5].…”

Section: Introductionmentioning

confidence: 99%

Bridging Molecular Mechanism and Clinical Practice in Vitiligo Treatment: An Updated Review

Ju,

Bae

2024

Dermatology

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Background: In recent years, a great advance has been made in the area of pathogenesis of vitiligo and the understanding of vitiligo treatment is also expanding. Summary: Treatment of vitiligo seeks to achieve three goals: cessation of disease progression, regeneration of pigmentation, and prevention of recurrence. To achieve these goals, a number of non-surgical interventions are available that suppress the autoimmune response and regenerate the remaining melanocytes from the reservoir, and optimal treatment outcome can be achieved when each modality is used properly. Key Messages: Our review describes various treatment modalities for vitiligo based on their molecular mechanism of action. Bridging the gap between molecular mechanisms and therapeutic options would be a valuable reference for physicians in clinical practice.

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Regulatory T Cells Require CCR6 for Skin Migration and Local Suppression of Vitiligo

Cited by 10 publications

References 46 publications

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients

Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers

Bridging Molecular Mechanism and Clinical Practice in Vitiligo Treatment: An Updated Review

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