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

Journal article

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.

Authors: Roberts, N; White, A; Jenkinson, W; Turchinovich, G; Nakamura, K

• Publication status: Published
• Journal: Immunity
• Volume: 36
• Issue: 3
• Pages: 427-437
• Publication date: 2012-03-15
• DOI: 10.1016/j.immuni.2012.01.016
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Fetus; Pregnancy; Signal Transduction; Precursor Cells, T-Lymphoid; Mice, Inbred C57BL; Animals; Receptor Activator of Nuclear Factor-kappa B; Female; Cell Differentiation; Receptors, Antigen, T-Cell, gamma-delta; Transcription Factors; Mice; Thymus Gland; Male; Epithelial Cells; Cellular Microenvironment; Mice, Knockout