Thymus transplantation is a promising therapy for the treatment
of DiGeorge syndrome-associated immunodeficiency [16], and a recent check details report, using postnatal allograft transplantation, hinted at the role of K14+ and human cTEC-marker CDR2-positive epithelial cells in the reconstitution of the thymus allograft [17]. Certainly, the next step would be the identification of the progenitor markers in the adult thymus as this would have practical implications for human thymus transplantation and for the restoration of T-cell immunocompetence. Despite the fact that the thymus starts involution soon after birth and becomes atrophic with age [18], the adult thymic epithelium is constantly regenerated from a pool of adult progenitor cells, albeit with decreasing PF-01367338 mw efficiency [7]. Thus, the capacity for renewed thymopoiesis is not lost with aging and could be restored therapeutically [19]. Different treatment strategies with growth factors (growth hormone, IGF-1, and FGF-7), IL-7 or sex steroids have been already applied in
diverse experimental systems to improve age-related loss of thymic function (reviewed in [20]). The differentiation of thymic epithelium shares features and markers with other epithelial tissues, including skin or mammary epithelial cells [21-23]. In this respect, lineage-tracing analysis of progenitor cells from mammary epithelium with cytokeratin promoters, has revealed the existence of a K14+ multi-potent progenitor at an early embryonic stage,
whereas postnatal and adult development are ensured by K14/K5+ and K8/K18+ unipotent stem cells that differentiate into myoepithelial and luminal lineages, respectively, and are no longer maintained by Tacrolimus (FK506) rare multi-potent progenitors [24]. The shift from bipotent stem cell prevalence at embryonic stage to unipotent or compartment-specific progenitors at postnatal and adult tissues may well take place in thymus too—the rapid turnover and the capacity to regenerate after the selective ablation indicate the potency of cTEC and mTEC lineage-specific progenitors in the postnatal and adult thymus [25, 26]. The study by Baik et al. [1] raises unanswered questions, namely the persistence of embryonic bipotent TEPCs and the relation of these TEPCs to the bi- or unipotent progenitors in the adult thymus. The cTEC/mTEC marker pattern, identified here, should be useful for further isolation and then characterization of the progenitors. Finally, the bipotent TEPC (and possible cTEC lineage progenitor) specificity for CD205, an endocytic C-type lectin-like molecule with a role in the recognition of apoptotic cells for antigen uptake and processing [27] warrants further characterization. The authors thank the European Regional Fund/Archimedes Foundation and the Estonian Research Council funding IUT2–2 for their support. The authors declare no financial or commercial conflict of interest.