Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire(+) Medullary Epithelium.

NA Roberts, Andrea White, William Jenkinson, G Turchinovich, Kyoko Nakamura, David Withers, Fiona McConnell, Guillaume Desanti, Cecile Benezech, SM Parnell, Adam Cunningham, M Paolino, JM Penninger, AK Simon, T Nitta, I Ohigashi, Y Takahama, Jorge Caamano, AC Hayday, Peter LaneEric Jenkinson, Graham Anderson

Research output: Contribution to journalArticle

115 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)427-437
Number of pages11
Issue number3
Publication statusPublished - 14 Mar 2012


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