title: FOXN1 recombinant protein enhances T-cell regeneration after hematopoietic stem cell transplantation in mice.
abstract: A prolonged period of T-cell recovery is the major challenge in hematopoietic stem cell transplantation (HSCT). Thymic epithelial cells (TECs) are the major component of the thymic microenvironment for T-cell generation. However, TECs undergo degeneration over time. FOXN1 plays a critical role in TEC development and is required to maintain adult TECs for thymopoiesis. To investigate the potential application of FOXN1, we have cloned and expressed recombinant FOXN1 protein (rFOXN1) that was fused with cell-penetrating peptides. We show here that the rFOXN1 protein can translocate from the cell surface into the cytoplasm and nucleus. Administration of rFOXN1 into both congenic and allogeneic HSCT recipient mice increased the number of TECs, resulting in enhanced thymopoiesis that led to an increased number of functional T cells in the periphery. The increased number of TECs is due to the enhanced survival and proliferation of TECs. Our results suggest that rFOXN1 has the potential to be used in enhancing T-cell regeneration in patients following HSCT.
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.|Department of Obstetrics and Gynecology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Di
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.|University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA.
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D012038:Regeneration; D013601:T-Lymphocytes / Q000166:cytology*; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; D011994:Recombinant Proteins; C090140:Whn protein
keywords: FOXN1; Hematopoietic stem cell transplantation; T-cell generation; Thymic epithelial cells; Thymus