title: Regenerative capacity of adult cortical thymic epithelial cells.
abstract: Involution of the thymus is accompanied by a decline in the number of thymic epithelial cells (TECs) and a severely restricted peripheral repertoire of T-cell specificities. TECs are essential for T-cell differentiation; they originate from a bipotent progenitor that gives rise to cells of cortical (cTEC) and medullary (mTEC) phenotypes, via compartment-specific progenitors. Upon acute selective near-total ablation during embryogenesis, regeneration of TECs fails, suggesting that losses from the pool of TEC progenitors are not compensated. However, it is unclear whether this is also true for the compartment-specific progenitors. The decline of cTECs is a prominent feature of thymic involution. Because cTECs support early stages of T-cell development and hence determine the overall lymphopoietic capacity of the thymus, it is possible that the lack of sustained regenerative capacity of cTEC progenitor cells underlies the process of thymic involution. Here, we examine this hypothesis by cell-type-specific conditional ablation of cTECs. Expression of the human diphtheria toxin receptor (hDTR) gene under the regulatory influence of the chemokine receptor Ccx-ckr1 gene renders cTECs sensitive to the cytotoxic effects of diphtheria toxin (DT). As expected, DT treatment of preadolescent and adult mice led to a dramatic loss of cTECs, accompanied by a rapid demise of immature thymocytes. Unexpectedly, however, the cTEC compartment regenerated after cessation of treatment, accompanied by the restoration of T-cell development. These findings provide the basis for the development of targeted interventions unlocking the latent regenerative potential of cTECs to counter thymic involution.
authors.affiliation: Department of Developmental Immunology,  Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg,  Germany.
authors.forename: Immanuel
authors.initials: I
authors.lastname: Rode
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
mesh_terms: D000367:Age Factors; D000728:Androgens / Q000502:physiology; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D016207:Cytokines / Q000502:physiology; D004167:Diphtheria Toxin / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009919:Orchiectomy; D009928:Organ Specificity; D011828:Radiation Chimera; D011944:Receptors, Androgen / Q000502:physiology; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D012727:Sex Characteristics; D060168:Thymocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D014770:Virilism / Q000139:chemically induced / Q000503:physiopathology; D000097628:Chemokine Receptor D6
chemical_list: D000728:Androgens; D016207:Cytokines; D004167:Diphtheria Toxin; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011944:Receptors, Androgen; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse