Migration of hematopoietic progenitors to the thymus

描述(申请人提供)：胸腺中的T细胞来自造血祖细胞。我们之前已经证明，祖细胞到胸腺的正常迁移使用两个归巢分子，CCR7和CCR9。然而，我们现在发现，在骨髓移植过程中，条件照射后祖细胞向胸腺的迁移不依赖CCR7和CCR9。出乎意料的是，我们发现抑制其他归巢分子可以显著改善骨髓移植后胸腺的重建。我们建议鉴定和鉴定正常胸腺和骨髓移植后归巢的祖细胞，鉴定和鉴定照射后祖细胞用于胸腺归巢的归巢分子。此外，我们将确定归巢分子的异位表达或抑制是否会允许更广泛的血祖细胞迁移到胸腺，并改善骨髓移植后的T淋巴细胞生成，并了解潜在的机制。好了！ 与公共卫生相关：归巢到胸腺的祖细胞的身份，以及细胞用来归巢到胸腺的归巢分子，还没有很好地理解。在这项建议中，我们将鉴定正常和骨髓移植后归巢到胸腺的细胞。我们将鉴定和鉴定胸腺归巢的分子，并确定归巢分子的异位表达是否会允许更广泛的血祖细胞迁移到胸腺，并改善骨髓移植后的T淋巴细胞生成。

DESCRIPTION (provided by applicant): T cells develop in the thymus from hematopoietic progenitors. We have previously shown that normal migration of progenitors to the thymus uses two homing molecules, CCR7 and CCR9. However, we have now found that progenitor migration to the thymus after conditioning irradiation during bone marrow transplantation is independent of CCR7 and CCR9. Unexpectedly, we find that inhibition of other homing molecules can dramatically improve thymic reconstitution after bone marrow transplantation. We propose to identify and characterize progenitors homing both the normal thymus and after bone marrow transplantation, to identify and characterize the homing molecules that are used by progenitors for thymic homing after irradiation. Further, we will determine whether the ectopic expresion or inhibition of homing molecules will allow a broader range of blood progenitors to migrate to the thymus and improve T lymphopoiesis after bone marrow transplantation, and understand what the underlying mechanisms might be. ! PUBLIC HEALTH RELEVANCE: The identity of progenitors homing to the thymus, and the homing molecules used by cells to get to the thymus, is not well understood. In this proposal, we will identify the cells homing to the thymus normally and after bone marrow transplantation. We will identify and characterize the molecules that are for thymic homing, and determine whether the ectopic expression of homing molecules will allow a broader range of blood progenitors to migrate to the thymus and improve T lymphopoiesis after bone marrow transplantation.