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

doi:10.1073/pnas.0810268105

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

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

210 Citations (Scopus)

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, CD8^loSirpα^hi/+ (CD8^loSirpα ⁺) and CD8^hiSirpα^lo/- (CD8 ^loSirpα^-), which have different origins. We found that the CD8^hiSirpα⁺ DCs represent a conventional DC subset that originates from the blood and migrates into the thymus. Moreover, we show that the CD8^loSirpα⁺ DCs demonstrate a superior capacity to induce T_Rs 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 T_R generation and negative selection.

Original language	English
Pages (from-to)	19869-19874
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	50
DOIs	https://doi.org/10.1073/pnas.0810268105
Publication status	Published - 16 Dec 2008
Externally published	Yes

Keywords

Migratory dendritic cells
Thymic selection
Tolerance

Access to Document

10.1073/pnas.0810268105

Link to publication in Scopus

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

Proietto, Anna I ; van Dommelen, Serani LH ; Zhou, Penghui ; Rizzitelli, Alexandra ; D'Amico, Angela ; Steptoe, Raymond J ; Naik, Shalin H. ; Lahoud, Mireille H. ; Liu, Yang ; Zheng, Pan ; Shortman, Ken ; Wu, Li. / Dendritic cells in the thymus contribute to T-regulatory cell induction. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 50. pp. 19869-19874.

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title = "Dendritic cells in the thymus contribute to T-regulatory cell induction",

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.",

keywords = "Migratory dendritic cells, Thymic selection, Tolerance",

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

year = "2008",

month = dec,

day = "16",

doi = "10.1073/pnas.0810268105",

language = "English",

volume = "105",

pages = "19869--19874",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Proietto, AI, van Dommelen, SLH, Zhou, P, Rizzitelli, A, D'Amico, A, Steptoe, RJ, Naik, SH, Lahoud, MH, 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, vol. 105, no. 50, pp. 19869-19874. https://doi.org/10.1073/pnas.0810268105

Dendritic cells in the thymus contribute to T-regulatory cell induction. / Proietto, Anna I; van Dommelen, Serani LH; Zhou, Penghui; Rizzitelli, Alexandra; D'Amico, Angela; Steptoe, Raymond J; Naik, Shalin H.; Lahoud, Mireille H.; Liu, Yang; Zheng, Pan; Shortman, Ken; Wu, Li.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 50, 16.12.2008, p. 19869-19874.

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

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AU - Proietto, Anna I

AU - van Dommelen, Serani LH

AU - Zhou, Penghui

AU - Rizzitelli, Alexandra

AU - D'Amico, Angela

AU - Steptoe, Raymond J

AU - Naik, Shalin H.

AU - Lahoud, Mireille H.

AU - Liu, Yang

AU - Zheng, Pan

AU - Shortman, Ken

AU - Wu, Li

PY - 2008/12/16

Y1 - 2008/12/16

N2 - 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.

AB - 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.

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