4.6 Review

Engineered antigen-specific regulatory T cells for autoimmune skin conditions

Journal

AUTOIMMUNITY REVIEWS
Volume 20, Issue 3, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.autrev.2021.102761

Keywords

Regulatory T cells; Antigen-specific; Autoimmune skin diseases; Chimeric antigen receptor; T cell receptor

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Funding

  1. National Institutes of Health [RO1s AR057643, CA191317]

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Regulatory T cells (Tregs) play a crucial role in autoimmune skin diseases, and alterations in their numbers and functions can lead to various conditions. The use of antigen-specific Tregs engineered cells shows promise in improving treatment efficacy, though challenges in clinical applications need to be addressed.
Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.

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