Rankl to boost thymic regeneration

Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoïesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, the inventors show that administration of RANK ligand (RANKL) after total body irradiation and BMT boosts thymic regeneration. Notably, this treatment is also beneficial upon BMT in aged individuals. The inventors show that RANKL can improve thymopoiesis in aged individuals affected by thymic involution. Finally, the inventors show that RANK receptor is conserved in the human thymus. Accordingly, one aspect of the present invention relates to a method of boosting thymic regeneration in a patient suffering from a thymic injury comprising administering to the subject a therapeutically effective amount of a RANKL polypeptide.

Keywords: RANKL, Thymic Regeneration, Bone Marrow Transplantation
Patent Application number: EP17 305 214.3
Inventors:
Magali IRLANoella LOPES
Publications:
EMBO Mol Med. 2017 Jun;9(6):835-851. doi: 10.15252/emmm.201607176

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