HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Henning, Steven W.; Fernández, Manuel F.; Mahon, James; Duff, Richard; Azarafrooz, Farshid; Guevara-Patiño, José A.; Rademaker, Alfred; Salzman, Andrew L.; Poole, I. Caroline Le

doi:10.1016/j.jid.2018.06.186

Cited by 37 publications

(31 citation statements)

References 40 publications

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“…This includes evaluating depigmentation, and the persistence of Tregs and melanocytes in the skin. Adoptive transfer of antigenspecific Tregs may offer an exciting opportunity to halt depigmentation and to complement up-and-coming therapeutics such as modified inducible HSP70 to tolerize dendritic cells (DCs) and Janus kinase (JAK) inhibitors to mitigate T cell activation (36,37).…”

Section: Introductionmentioning

confidence: 99%

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

et al. 2020

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Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo. CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.

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Section: Introductionmentioning

confidence: 99%

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

et al. 2020

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“…The same research team then confirmed their initial results in the Sinclair swine model that develops melanomas regressing by immune surveillance, leading to vitiligo-like depigmentation. The findings of this subsequent study showed that treating swine with HSP70iQ435A-encoding DNA induced repigmentation of treated lesions and, most importantly, of distant vitiligo lesions, indicating a possible systemic effect [14]. This approach seems to confer a long-lasting repigmentation.…”

Section: Targeting Innate Immunitymentioning

confidence: 74%

Vitiligo, From Physiopathology to Emerging Treatments: A Review

Migayron

Boniface

Sénéschal

2020

Dermatol Ther (Heidelb)

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Vitiligo is a chronic inflammatory skin disease leading to the loss of epidermal melanocytes. To date, treatment options for vitiligo patients are limited, lack sustained efficacy, and are mainly based on off-label use of immunosuppressive agents, such as systemic or topical steroids or topical calcineurin inhibitors, in association with the use of ultraviolet light. However, recent insights into the understanding of the immune pathogenesis of the disease have led to the identification of several therapeutic targets and the development of targeted therapies that are now being tested in clinical trials. In this review, based on the physiopathology of the disease, we summarize emerging targets that could be developed for the treatment of vitiligo and discuss recent and ongoing developments of drugs for the management of the disease.

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“…A modified version of Hsp70i, Hsp70i Q435A , a reversed depigmentation that was identified in Sinclair Swine recently, has also been observed in mice models, thus providing the rationale for study in human species. Mutant Hsp70i opens a door to potential new treatment for vitiligo patients [39].…”

Section: Innate Immunity Bridges the Gap Between Oxidative Stress Andmentioning

confidence: 99%

Perspectives of New Advances in the Pathogenesis of Vitiligo: From Oxidative Stress to Autoimmunity

2019

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Vitiligo is an autoimmune cutaneous disease in which melanocytes are destroyed by CD8 + T cells resulting in disfiguring white spots. From the very beginning of the disease, oxidative stress plays a significant role in promoting the onset of vitiligo, as noted by many studies. Multiple factors lead to the overproduction of reactive oxygen species (ROS), and collaboratively cause ROS accumulation in vulnerable melanocytes. However, ROS are responsible for melanocyte damage manifested by the level of molecules, organelles, and cells, and the generation of autoantigens, through different pathways related to the dysregulation of melanocytes. Recent studies have shown that presentation of autoantigens is mediated by innate immunity, which bridges the gap between oxidative stress and adaptive immunity. The recruitment of CD8 + T cells induced by cytokines and chemokines guarantees the final destruction of epidermal melanocytes. Moreover, emerging concerns regarding regulatory T cells and resident memory T cells help explain the reinstatement and relapse of vitiligo. Here, we provide new perspectives in the advances in understanding of this disease pathogenesis and we attempt to find more interrelationships between oxidative stress and autoimmunity.

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HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Cited by 37 publications

References 40 publications

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

Vitiligo, From Physiopathology to Emerging Treatments: A Review

Perspectives of New Advances in the Pathogenesis of Vitiligo: From Oxidative Stress to Autoimmunity

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