NKT1的胸腺内分化调节和移植物抗宿主病对NKT1分化的影响研究

Invariant natural killer T cells （iNKTs）是识别CD1d呈递的糖脂类抗原的αβ T细胞，能够对刺激产生快速应答，在多种生理和病理过程中发挥重要作用。iNKT细胞在胸腺内完成发育和部分功能亚群的分化，但其分化调节还存在很多未知之处。我们基于对胸腺内不成熟iNKT的单细胞测序结果以及对NKT1分化调节的前期结果，推测NKT1在定向分化后还存在功能成熟的中间阶段，胸腺髓质微环境在该阶段的成熟过程中发挥重要的调节作用。我们拟鉴定和探讨NKT1的分化中间阶段及其特点，并从I型干扰素角度和利用伴有移植物抗宿主病的单倍型相合骨髓移植模型探讨胸腺髓质微环境对NKT1功能成熟的影响及其机制。研究结果将有助于深入理解iNKT细胞功能亚群分化和成熟的调控机制和意义，为促进造血干细胞移植后的iNKT细胞重建以及以iNKT为基础的细胞治疗方案的优化提供新的思路和方法。

Invariant natural killer T cells (iNKTs) are αβ T cells that recognize glycolipids presented by CD1d molecule. iNKT cells make fast responses to multiple stimuli and play crucial roles in many physiological and pathological processes. The regulation of iNKT cell development and differentiation in the thymus remains not well understood. Based on single-cell RNA sequencing results of thymic immature iNKT cells, we hypothesize the existence of an intermediate developmental stage in the thymus between NKT1 commitment and functional maturation of IFN-γ producing NKT1 cells. The thymic medullary microenvironment is crucial in regulating the development of this intermediate stage. We will characterize this intermediate stage of NKT1 cells. We will also investigate the role of medulla-derived type I interferon on NKT1 differentiation and the impact of graft-versus-host disease on NKT1 maturation in thymic medulla. The results will shed light on better understanding of the regulation of iNKT cell functional maturation and facilitating iNKT cell reconstitution and iNKT-based immune cell therapy.