Lymph nodes (LNs) are at the cross roads of immunity and tolerance. These tissues are compartmentalized into specialized niche areas by lymph node stromal cells (LN SCs). LN SCs shape the LN microenvironment and guide immunological cells into different zones through establishment of a CCL19 and CCL21 gradient. Following local immunological cues, LN SCs modulate activity to support immune cell priming, activation, and fate. This review will present our current understanding of LN SC subsets roles in regulating T cell tolerance. Three major types of LN SC subsets, namely fibroblastic reticular cells, lymphatic endothelial cells, and blood endothelial cells, are discussed. These subsets serve as scaffolds to support and regulate T cell homeostasis. They contribute to tolerance by presenting peripheral tissue antigens to both CD4 and CD8 T cells. The role of LN SCs in regulating T cell migration and tolerance induction is discussed. Looking forward, recent advances in bioengineered materials and approaches to leverage LN SCs to induce T cell tolerance are highlighted, as are current clinical practices that allow for manipulation of the LN microenvironment to induce tolerance. Increased understanding of LN architecture, how different LN SCs integrate immunological cues and shape immune responses, and approaches to induce T cell tolerance will help further combat autoimmune diseases and graft rejection.

中文翻译：

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淋巴结基质和微环境在 T 细胞耐受中的作用。

淋巴结 (LN) 处于免疫和耐受的十字路口。这些组织被淋巴结基质细胞 (LN SCs) 划分为专门的生态位区域。LN SCs 通过建立 CCL19 和 CCL21 梯度来塑造 LN 微环境并引导免疫细胞进入不同的区域。根据局部免疫提示，LN SCs 调节活性以支持免疫细胞启动、激活和命运。本综述将介绍我们目前对 LN SC 亚群在调节 T 细胞耐受性中的作用的理解。讨论了三种主要类型的 LN SC 亚群，即成纤维细胞网状细胞、淋巴管内皮细胞和血液内皮细胞。这些亚群作为支架来支持和调节 T 细胞稳态。它们通过将外周组织抗原呈递给 CD4 和 CD8 T 细胞来促进耐受。讨论了 LN SCs 在调节 T 细胞迁移和耐受诱导中的作用。展望未来，生物工程材料和利用 LN SCs 诱导 T 细胞耐受性的方法的最新进展被强调，目前的临床实践允许操纵 LN 微环境以诱导耐受性。加深对 LN 结构的了解，不同的 LN SCs 如何整合免疫线索和塑造免疫反应，以及诱导 T 细胞耐受的方法将有助于进一步对抗自身免疫性疾病和移植物排斥。就像目前允许操纵 LN 微环境以诱导耐受性的临床实践一样。加深对 LN 结构的了解，不同的 LN SCs 如何整合免疫线索和塑造免疫反应，以及诱导 T 细胞耐受的方法将有助于进一步对抗自身免疫性疾病和移植物排斥。就像目前允许操纵 LN 微环境以诱导耐受性的临床实践一样。加深对 LN 结构的了解，不同的 LN SCs 如何整合免疫线索和塑造免疫反应，以及诱导 T 细胞耐受的方法将有助于进一步对抗自身免疫性疾病和移植物排斥。