title: Role of Bone Marrow Maturity, Insulin-Like Growth Factor 1 Receptor, and Forkhead Box Protein N1 in Thymic Involution and Rejuvenation.
abstract: Thymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 (FOXN1) as well as bone marrow (BM) in thymic rejuvenation and involution. We examined thymic rejuvenation and involution by means of histology and flow cytometry. Thymic function was assessed by the ability to induce tolerance of allogeneic kidneys. Aged thymi were rejuvenated in a juvenile environment, and successfully induced organ tolerance, while juvenile thymi in aged recipients involuted and had a limited ability to induce tolerance. However, juvenile BM inhibited the involution process of juvenile thymi in aged recipients. An elevated expression of both FOXN1 and IGF1 receptors (IGF-1R) was observed in juvenile thymi and rejuvenated thymi. Juvenile BM plays a role in promoting the local thymic milieu as indicated by its ability to inhibit thymic involution in aged animals. The expression of FOXN1 and IGF-1R was noted to increase under conditions that stimulated rejuvenation, suggesting that these factors are involved in thymic recovery.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: V
authors.initials: V
authors.lastname: Villani
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Sekijima
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: I M
authors.initials: IM
authors.lastname: Hanekamp
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: J S
authors.initials: JS
authors.lastname: Hanekamp
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: T A
authors.initials: TA
authors.lastname: Cormack
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: S G
authors.initials: SG
authors.lastname: Moran
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Kawai
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Columbia Center for Translational Research, Columbia University Medical Center, New York, NY.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.|Columbia Center for Translational Research, Columbia University Medical Center, New York, NY.
authors.forename: K
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006085:Graft Survival; D007108:Immune Tolerance; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D012060:Rejuvenation / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D013950:Thymus Gland / Q000502:physiology* / Q000637:transplantation
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein; D017526:Receptor, IGF Type 1
keywords: animal models: porcine; basic (laboratory) research/science; bone marrow/hematopoietic stem cell transplantation; immunobiology; kidney transplantation/nephrology; thymus/thymic biology; tolerance: experimental; translational research/science