1. Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium.
- Author
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Ohigashi I, White AJ, Yang MT, Fujimori S, Tanaka Y, Jacques A, Kiyonari H, Matsushita Y, Turan S, Kelly MC, Anderson G, and Takahama Y
- Subjects
- Mice, Animals, Mice, Inbred C57BL, Thymus Gland metabolism, Cell Differentiation, Epithelial Cells metabolism, Epithelium metabolism, Thymocytes metabolism, Transcription Factors genetics, Transcription Factors metabolism
- Abstract
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here, we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny in mice. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium., Competing Interests: IO, AW, MY, SF, YT, AJ, HK, YM, ST, MK, GA, YT No competing interests declared
- Published
- 2024
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