Dendritic cells in the thymus contribute to T-regulatory cell induction

Anna I Proietto, Serani LH van Dommelen, Penghui Zhou, Alexandra Rizzitelli, Angela D'Amico, Raymond J Steptoe, Shalin H. Naik, Mireille H. Lahoud, Yang Liu, Pan Zheng, Ken Shortman, Li Wu

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Abstract

Central tolerance is established through negative selection of self-reactive thymocytes and the induction of T-regulatory cells (T Rs). The role of thymic dendritic cells (TDCs) in these processes has not been clearly determined. In this study, we demonstrate that in vivo, TDCs not only play a role in negative selection but in the induction of T Rs. TDCs include two conventional dendritic cell (DC) subtypes, CD8loSirpαhi/+ (CD8loSirpα +) and CD8hiSirpαlo/- (CD8 loSirpα-), which have different origins. We found that the CD8hiSirpα+ DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8loSirpα+ DCs demonstrate a superior capacity to induce TRs in vitro. Finally, using a thymic transplantation system, we demonstrate that the DCs in the periphery can migrate into the thymus, where they efficiently induce TR generation and negative selection.

Original languageEnglish
Pages (from-to)19869-19874
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number50
DOIs
Publication statusPublished - 16 Dec 2008
Externally publishedYes

Keywords

  • Migratory dendritic cells
  • Thymic selection
  • Tolerance

Cite this

Proietto, A. I., van Dommelen, S. LH., Zhou, P., Rizzitelli, A., D'Amico, A., Steptoe, R. J., Naik, S. H., Lahoud, M. H., Liu, Y., Zheng, P., Shortman, K., & Wu, L. (2008). Dendritic cells in the thymus contribute to T-regulatory cell induction. Proceedings of the National Academy of Sciences of the United States of America, 105(50), 19869-19874. https://doi.org/10.1073/pnas.0810268105