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Publication : Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice.

First Author  Zhang SL Year  2014
Journal  Blood Volume  124
Issue  2 Pages  296-304
PubMed ID  24876562 Mgi Jnum  J:214377
Mgi Id  MGI:5602894 Doi  10.1182/blood-2014-01-552794
Citation  Zhang SL, et al. (2014) Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice. Blood 124(2):296-304
abstractText  Development of T cells in the thymus requires continuous importation of T-lineage progenitors from the bone marrow via the circulation. Following bone marrow transplant, recovery of a normal peripheral T-cell pool depends on production of naive T cells in the thymus; however, delivery of progenitors to the thymus limits T-lineage reconstitution. Here, we examine homing of intravenously delivered progenitors to the thymus following irradiation and bone marrow reconstitution. Surprisingly, following host conditioning by irradiation, we find that homing of lymphoid-primed multipotent progenitors and common lymphoid progenitors to the thymus decreases more than 10-fold relative to unirradiated mice. The reduction in thymic homing in irradiated mice is accompanied by a significant reduction in CCL25, an important chemokine ligand for thymic homing. We show that pretreatment of bone marrow progenitors with CCL25 and CCL21 corrects the defect in thymic homing after irradiation and promotes thymic reconstitution. These data suggest new therapeutic approaches to promote T-cell regeneration.
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