血液造血干细胞移植中存在的挑战，如骨髓植入低、移植物抗宿主病（GvHD）和长期免疫抑制的需求，可以通过组织内的T调节细胞（Tregs）解决，例如骨髓Tregs。在血液造血干细胞移植中控制不良免疫反应，最小化由于长期免疫抑制而导致的感染和继发癌症等相关风险是这一领域临床实践的关键方面。虽然系统性免疫抑制治疗可以在大多数患者中实现合理的GvHD控制，但相关的副作用仍然是主要限制因素。开发更有针对性的免疫抑制策略是一个未满足的临床需求，并是数个正在进行的研究项目的焦点。Tregs是CD4+ T细胞的不可替代的亚群，对控制免疫稳态至关重要。已知在自身免疫疾病中，Tregs的数量和功能都会降低。由于Tregs可以在体外扩增并注入患者，因此这些细胞成为细胞治疗产品备受关注。这些试验发现Treg疗法安全、耐受性好，并具有一些早期的疗效迹象。然而，Tregs是T细胞的多样性亚群，近年来已经发现了几个新的亚群，超越了传统的胸腺性（tTregs）和外围性（pTregs）。越来越多的证据表明，存在着组织特异性的定居和组织特异性Tregs。骨髓（BM）Tregs就是定居于组织中的Tregs之一。BM Tregs丰富在骨髓内，发挥着免疫抑制和维持造血干细胞（HSCs）的双重作用。通过直接抑制HSCs分化、维持一个增殖的HSCs池以及促进支持HSCs的功能性基质细胞的发展来实现HSCs的维护。本文评述了Tregs的生物学，重点关注其发展和多样性。我们将集中讨论BM Tregs的生物学和治疗潜力，重点介绍它们在HSCT中的应用。版权所有 © 2022 The Authors。由Elsevier Ltd.发表。保留所有权利。

Challenges in haematopoietic stem cell transplantation such as low bone marrow (BM) engraftment, graft versus host disease (GvHD) and the need for long-term immunosuppression could be addressed using T regulatory cells (Tregs) resident in the tissue of interest, in this case, BM Tregs. Controlling the adverse immune response in haematopoietic stem cell transplantation (HSCT) and minimising the associated risks such as infection and secondary cancers due to long-term immunosuppression is a crucial aspect of clinical practice in this field. While systemic immunosuppressive therapy could achieve reasonable GvHD control in most patients, related side effects remain the main limiting factor. Developing more targeted immunosuppressive strategies is an unmet clinical need and is the focus of several ongoing research projects. Tregs are a non-redundant sub-population of CD4+ T cells essential for controlling the immune homeostasis. Tregs are known to be reduced in number and function in autoimmune conditions. There is considerable interest in these cells as cell therapy products since they can be expanded in vitro and infused into patients. These trials have found Treg therapy to be safe, well-tolerated, and with some early signs of efficacy. However, Tregs are a heterogeneous subpopulation of T cells, and several novel subpopulations have been identified in recent years beyond the conventional thymic (tTregs) and peripheral (pTregs). There is increasing evidence for the presence of resident and tissue-specific Tregs. Bone marrow (BM) Tregs are one example of tissue-resident Tregs. BM Tregs are enriched within the marrow, serving a dual function of immunosuppression and maintenance of haematopoietic stem cells (HSCs). HSCs maintenance is achieved through direct suppression of HSCs differentiation, maintaining a proliferating pool of HSCs, and promoting the development of functional stromal cells that support HSCs. In this review, we will touch upon the biology of Tregs, focusing on their development and heterogeneity. We will focus on the BM Tregs from their biology to their therapeutic potential, focusing on their use in HSCT.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.