| Summary: | 碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 99 === Interleukin 15 (IL-15) is a multi-function cytokine that regulates the activation and homeostasis of memory CD8 T cells, NK cells, NKT cells and intestinal intraepithelial lymphocytes (iIEL). Our lab found that aged Il15rα -/- and Il15-/- mice produce autoantibodies (ANA) and are impaired in thymocyte negative selection. The expression of IL-15 system by thymic epithelial cells (TECs) and dendritic cells (DC) are required for thymocyte negative selection. My project is to characterize TECs and stromal cells of WT, Il15rα -/- and Il15-/- mice, including cellularity, APC (antigen presenting cell)-associated marker expression, and Aire expression. I found that the number of total TECs and mTECs declines in KO thymus but not in WT thymus, while the expression of APC-associated markers and Aire were comparable between WT and KO TECs. The number of CD45- stromal cells and cTECs decreases in Il15-/- thymus. To investigate the ANA arising in aged KO mice, we compared TECs in aged WT and KO thymus, but did not find differences in the examined features. Then, we compare these properties between young and aged TECs and stromal cells. The cell number of stromal cells, mTECs and Aire+ mTECs largely decreases but cTECs increases in aged thymus than that of young thymus. The expression level of MHC-II decreases, but CD86 increases in aged TECs. The enormous changes in aged thymus may influence central tolerance formation. Besides, We also examined the frequency, cell numbers and Foxp3 expression of WT and KO splenic Tregs in young and aged mice, which are associated with the maintainence of tolerance. The expression level of Foxp3 is lower in KO and aged mice than that of WT mice.
My work will advance our understanding in how the IL-15 system regulates thymocyte negative selection via regulating properties of mTECs. The part of aging investigation provides an accurate analysis of TECs in atrophic thymus, which may explain certain dysfunction of aged thymus.
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