Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium

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 C Hayday, Peter J L LaneEric J Jenkinson, Graham Anderson

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)427-37
Number of pages11
JournalImmunity
Volume36
Issue number3
DOIs
Publication statusPublished - 23 Mar 2012

Keywords

  • Animals
  • Cell Differentiation
  • Cellular Microenvironment
  • Epithelial Cells
  • Female
  • Fetus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, T-Lymphoid
  • Pregnancy
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Antigen, T-Cell, gamma-delta
  • Signal Transduction
  • Thymus Gland
  • Transcription Factors

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