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| Item Type: | Article |
|---|---|
| Title: | Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium |
| Creators Name: | Roberts, N.A., White, A.J., Jenkinson, W.E., Turchinovich, G., Nakamura, K., Withers, D.R., McConnell, F.M., Desanti, G.E., Benezech, C., Parnell, S.M., Cunningham, A.F., Paolino, M., Penninger, J.M., Simon, A.K., Nitta, T., Ohigashi, I., Takahama, Y., Caamano, J.H., Hayday, A.C., Lane, P.J.L., Jenkinson, E.J. and Anderson, G. |
| Abstract: | The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant Vγ5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5(+) γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation. |
| Keywords: | AIRE Protein, Cell Differentiation, Cellular Microenvironment, Epithelial Cells, Fetus, Inbred C57BL Mice, Knockout Mice, T-Lymphoid Precursor Cells, Pregnancy, Receptor Activator of Nuclear Factor-kappa B, gamma-delta T-Cell Antigen Receptors, Signal Transduction, Thymus Gland, Transcription Factors, Animals, Mice |
| Source: | Immunity |
| ISSN: | 1074-7613 |
| Publisher: | Elsevier / Cell Press |
| Volume: | 36 |
| Number: | 3 |
| Page Range: | 427-37 |
| Date: | 23 March 2012 |
| Official Publication: | https://doi.org/10.1016/j.immuni.2012.01.016 |
| PubMed: | View item in PubMed |
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