Dkk1 mediated inhibition of Wnt Signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration (36.32)

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (1_Supplement), p.36-36.32
• Main Authors: Pezzano, Mark, Osada, Masako, Jardine, Logan, Misir, Ruth, Andl, Thomas, Millar, Sarah
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.36.32

The molecular mechanisms, which control both the initial development and subsequent maintenance of TEC microenvironments, are poorly defined. Regulation of Wnt signaling has been shown to impact both early thymocyte and thymic epithelial development. Early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of Wnt signaling in the maintenance of TECs in the postnatal thymus. Tetracycline-regulated expression of the Wnt inhibitor DKK1 in cTECs and mTECs of adult mice, results in rapid thymic degeneration characterized by a reduced Foxn1 expression, loss of K5K8DP putative TEC progenitors, decreased proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments. The results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic degeneration associated bone marrow transplants.