As the primary site for T cell development, the thymus is responsible for the production and selection of a functional, yet self-tolerant T cell repertoire. This critically depends on thymic stromal cells, derived from the pharyngeal apparatus during embryogenesis. Thymic epithelial cells, mesenchymal and vascular elements together form the unique and highly specialised microenvironment required to support all aspects of thymopoiesis and T cell central tolerance induction. Although rare, inborn errors of thymic stromal cells constitute a clinically important group of conditions because their immunological consequences, which include autoimmune disease and T cell immunodeficiency, can be life-threatening if unrecognised and untreated. In this review, we describe the molecular and environmental aetiologies of the thymic stromal cell defects known to cause disease in humans, placing particular emphasis on those with a propensity to cause thymic hypoplasia or aplasia and consequently severe congenital immunodeficiency. We discuss the principles underpinning their diagnosis and management, including the use of novel tools to aid in their identification and strategies for curative treatment, principally transplantation of allogeneic thymus tissue.

胸腺作为T细胞发育的主要部位，负责产生和选择功能性但自我耐受的T细胞库。这主要取决于在胚胎发生过程中源自咽部装置的胸腺基质细胞。胸腺上皮细胞，间充质和血管成分共同形成了支持胸腺细胞生成和T细胞中枢耐受诱导各个方面所需的独特且高度专业化的微环境。胸腺基质细胞的先天性错误虽然很少见，但在临床上却构成了一组重要的疾病，因为如果不加以识别和治疗，它们的免疫学后果（包括自身免疫性疾病和T细胞免疫缺陷）可能会危及生命。在这篇评论中 我们描述了已知会导致人类疾病的胸腺基质细胞缺陷的分子和环境病因，特别着重于容易引起胸腺发育不全或发育不良并因此导致严重的先天性免疫缺陷的患者。我们讨论了支持其诊断和管理的原理，包括使用新颖的工具帮助其识别和治疗策略，主要是同种异体胸腺组织的移植。