Engineered antigen-specific regulatory T cells for autoimmune skin conditions

Zhussipbek Mukhatayev, Yekaterina O. Ostapchuk, Deyu Fang, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number102761
JournalAutoimmunity Reviews
Volume20
Issue number3
DOIs
StatePublished - Mar 2021

Funding

This work was supported in part by National Institutes of Health (grant numbers RO1s AR057643, CA191317) grants to I.C.L.P.

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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