Rank signaling links the development of invariant γδ T cell progenitors and Aire+ medullary epithelium
Authors list
Natalie A Roberts Andrea J White William E Jenkinson Gleb Turchinovich Kyoko Nakamura David R Withers Fiona M McConnell Guillaume E Desanti Cecile Benezech Sonia M Parnell Adam F Cunningham Magdalena Paolino Josef M Penninger Anna Katharina Simon Takeshi Nitta Izumi Ohigashi Yousuke Takahama Jorge H Caamano Adrian Hayday Peter JL Lane Eric J Jenkinson Graham AndersonAbstract
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.
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Publisher website (DOI) 10.1016/j.immuni.2012.01.016
Europe PubMed Central 22425250
Pubmed 22425250
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