Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary Epithelium
نویسندگان
چکیده
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.
منابع مشابه
Rank Signaling Links the Development of Invariant gd T Cell Progenitors and Aire Medullary Epithelium
Citation for published version: Roberts, NA, White, AJ, Jenkinson, WE, Turchinovich, G, Nakamura, K, Withers, DR, McConnell, FM, Desanti, GE, Benezech, C, Parnell, SM, Cunningham, AF, Paolino, M, Penninger, JM, Simon, AK, Nitta, T, Ohigashi, I, Takahama, Y, Caamano, JH, Hayday, AC, Lane, PJL, Jenkinson, EJ & Anderson, G 2012, 'Rank signaling links the development of invariant T cell progenitors...
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