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Induced regulatory T cells as immunotherapy in allotransplantation and autoimmunity: challenges and opportunities

生物 自身免疫 同种异体移植 肿瘤免疫学 免疫疗法 免疫学 调节性T细胞 免疫系统 移植 T细胞 内科学 医学 白细胞介素2受体
作者
Evelyn Katy Alvarez-Salazar,Arimelek Cortés-Hernández,Saúl Arteaga-Cruz,Gloria Soldevila
出处
期刊:Journal of Leukocyte Biology [Wiley]
卷期号:116 (5): 947-965 被引量:1
标识
DOI:10.1093/jleuko/qiae062
摘要

Abstract Regulatory T cells play a crucial role in the homeostasis of the immune response. Regulatory T cells are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the regulatory T-cell master transcription factor. In addition, regulatory T cells can be induced from naive CD4+ T cells to express Foxp3 under specific conditions both in vivo (peripheral regulatory T cells) and in vitro (induced regulatory T cells). Both subsets of thymic regulatory T cells and peripheral regulatory T cells are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that induced regulatory T cells may be less stable compared to regulatory T cells, mainly due to epigenetic differences, accumulating evidence in animal models shows that induced regulatory T cells are stable in vivo and can be used for the treatment of inflammatory disorders, including autoimmune diseases and allogeneic transplant rejection. In this review, we describe the biological characteristics of induced regulatory T cells, as well as the key factors involved in induced regulatory T-cell transcriptional, metabolic, and epigenetic regulation, and discuss recent advances for de novo generation of stable regulatory T cells and their use as immunotherapeutic tools in different experimental models. Moreover, we discuss the challenges and considerations for the application of induced regulatory T cells in clinical trials and describe the new approaches proposed to achieve in vivo stability, including functional or metabolic reprogramming and epigenetic editing.

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