Migration of hematopoietic progenitors to the thymus

描述（由申请人提供）：T细胞在胸腺中从造血祖细胞发育而来。我们以前已经表明，正常迁移的祖细胞胸腺使用两个归巢分子，CCR 7和CCR 9。然而，我们现在已经发现，在骨髓移植过程中，在条件照射后祖细胞迁移到胸腺是独立于CCR7和CCR9的。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的胸腺重建。我们建议识别和表征正常胸腺和骨髓移植后的祖细胞归巢，识别和表征辐射后胸腺归巢的祖细胞所使用的归巢分子。此外，我们将确定是否异位表达或抑制归巢分子将允许更广泛的血液祖细胞迁移到胸腺和改善骨髓移植后的T淋巴细胞生成，并了解潜在的机制可能是什么。! 公共卫生相关性：归巢到胸腺的祖细胞的身份，以及细胞用来到达胸腺的归巢分子，还没有很好的理解。在这个计划中，我们将鉴定正常和骨髓移植后归巢到胸腺的细胞。我们将鉴定和表征胸腺归巢的分子，并确定归巢分子的异位表达是否允许更广泛的血液祖细胞迁移到胸腺，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.