已知造血系统中祖细胞的异常分化会严重影响宿主的免疫反应。在此，我们证明 NOD1（细菌肽聚糖的胞质先天传感器）也在小鼠造血细胞中发挥作用，作为淋巴祖细胞的生成和分化以及外周 T 淋巴细胞稳态的主要调节因子。我们进一步表明，NOD1 通过促进造血细胞因子下游的 STAT5 信号传导来介导这些功能。在稳态下，NOD1 的缺失导致成熟 T、B 和自然杀伤细胞数量适度但显着减少。在全身性原生动物感染期间，这种缺陷显着增强，导致宿主死亡。功能性 NOD1 的缺乏还会损害 T 细胞依赖性抗肿瘤免疫，同时预防结肠炎。这些发现表明，除了作为细菌配体受体的经典作用外，NOD1 通过与主要宿主细胞因子信号通路相互作用，在调节适应性免疫方面发挥着重要作用。© 2023。这是美国政府的作品，不受版权保护在美国;外国版权保护可能适用。

Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a cytosolic innate sensor of bacterial peptidoglycan, also functions in murine hematopoietic cells as a major regulator of both the generation and differentiation of lymphoid progenitors as well as peripheral T lymphocyte homeostasis. We further show that NOD1 mediates these functions by facilitating STAT5 signaling downstream of hematopoietic cytokines. In steady-state, loss of NOD1 resulted in a modest but significant decrease in numbers of mature T, B and natural killer cells. During systemic protozoan infection this defect was markedly enhanced, leading to host mortality. Lack of functional NOD1 also impaired T cell-dependent anti-tumor immunity while preventing colitis. These findings reveal that, in addition to its classical role as a bacterial ligand receptor, NOD1 plays an important function in regulating adaptive immunity through interaction with a major host cytokine signaling pathway.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.