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. Lane; Eric J. Jenkinson; Graham Anderson

doi:10.1016/j.immuni.2012.01.016

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

Peter Gorer Department of Immunobiology

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

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 language	English
Pages (from-to)	427-437
Number of pages	11
Journal	Immunity
Volume	36
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2012.01.016
Publication status	Published - 23 Mar 2012

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Roberts, N. A., White, A. J., Jenkinson, W. E., Turchinovich, G., Nakamura, K., Withers, D. R., McConnell, F. M., Desanti, G. E., Benezech, C., Parnell, S. M., Cunningham, A. F., Paolino, M., Penninger, J. M., Simon, A. K., Nitta, T., Ohigashi, I., Takahama, Y., Caamano, J. H., Hayday, A. C., ... Anderson, G. (2012). Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium. Immunity, 36(3), 427-437. https://doi.org/10.1016/j.immuni.2012.01.016

@article{749c9b84fda54a908955e56dcced4d46,

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

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.",

author = "Roberts, {Natalie A.} and White, {Andrea J.} and Jenkinson, {William E.} and Gleb Turchinovich and Kyoko Nakamura and Withers, {David R.} and McConnell, {Fiona M.} and Desanti, {Guillaume E.} and Cecile Benezech and Parnell, {Sonia M.} and Cunningham, {Adam F.} and Magdalena Paolino and Penninger, {Josef M.} and Simon, {Anna Katharina} and Takeshi Nitta and Izumi Ohigashi and Yousuke Takahama and Caamano, {Jorge H.} and Hayday, {Adrian C.} and Lane, {Peter J. L.} and Jenkinson, {Eric J.} and Graham Anderson",

year = "2012",

month = mar,

day = "23",

doi = "10.1016/j.immuni.2012.01.016",

language = "English",

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pages = "427--437",

journal = "Immunity",

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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 γδ T cell progenitors and Aire(+) medullary epithelium', Immunity, vol. 36, no. 3, pp. 427-437. https://doi.org/10.1016/j.immuni.2012.01.016

TY - JOUR

T1 - Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium

AU - Roberts, Natalie A.

AU - White, Andrea J.

AU - Jenkinson, William E.

AU - Turchinovich, Gleb

AU - Nakamura, Kyoko

AU - Withers, David R.

AU - McConnell, Fiona M.

AU - Desanti, Guillaume E.

AU - Benezech, Cecile

AU - Parnell, Sonia M.

AU - Cunningham, Adam F.

AU - Paolino, Magdalena

AU - Penninger, Josef M.

AU - Simon, Anna Katharina

AU - Nitta, Takeshi

AU - Ohigashi, Izumi

AU - Takahama, Yousuke

AU - Caamano, Jorge H.

AU - Hayday, Adrian C.

AU - Lane, Peter J. L.

AU - Jenkinson, Eric J.

AU - Anderson, Graham

PY - 2012/3/23

Y1 - 2012/3/23

N2 - 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.

AB - 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.

U2 - 10.1016/j.immuni.2012.01.016

DO - 10.1016/j.immuni.2012.01.016

M3 - Article

C2 - 22425250

VL - 36

SP - 427

EP - 437

JO - Immunity

JF - Immunity

IS - 3

ER -

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

Abstract

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