Eomesodermin promotes the development of type 1 regulatory T (TR1) cells

Ping Zhang; Jason S. Lee; Kate H. Gartlan; Iona S. Schuster; Iain Comerford; Antiopi Varelias; Md Ashik Ullah; Slavica Vuckovic; Motoko Koyama; Rachel D. Kuns; Kelly R. Locke; Kirrilee J. Beckett; Stuart D. Olver; Luke D. Samson; Marcela Montes de Oca; Fabian de Labastida Rivera; Andrew D. Clouston; Gabrielle T. Belz; Bruce R. Blazar; Kelli P. MacDonald; Shaun R. McColl; Ranjeny Thomas; Christian R. Engwerda; Mariapia A. Degli-Esposti; Axel Kallies; Siok Keen Tey; Geoffrey R. Hill

doi:10.1126/sciimmunol.aah7152

Eomesodermin promotes the development of type 1 regulatory T (T_R1) cells

Ping Zhang, Jason S. Lee, Kate H. Gartlan, Iona S. Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D. Kuns, Kelly R. Locke, Kirrilee J. Beckett, Stuart D. Olver, Luke D. Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D. Clouston, Gabrielle T. Belz, Bruce R. Blazar, Kelli P. MacDonaldShaun R. McColl, Ranjeny Thomas, Christian R. Engwerda, Mariapia A. Degli-Esposti, Axel Kallies, Siok Keen Tey, Geoffrey R. Hill

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

113 Scopus citations

Abstract

Type 1 regulatory T (T_R1) cells are Foxp3⁻ interleukin-10 (IL-10)–producing CD4⁺ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that T_R1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for T_R1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in T_R1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of T_R1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.

Original language	English (US)
Article number	eaah7152
Journal	Science Immunology
Volume	2
Issue number	10
DOIs	https://doi.org/10.1126/sciimmunol.aah7152
State	Published - 2017

Bibliographical note

Funding Information:
We thank P. Hall, M. Rist, and G. Chojnowski for expert cell sorting and the animal facilities of QIMR Berghofer Medical Research Institute and M. Flynn for expert graphical work. This work was supported by research grants held by G.R.H. from the National Health and Medical Research Council (NHMRC; Australia). B.R.B. is supported by funds from the NIH (R01 AI34495, R01 HL56067, and AI 11879). C.R.E. is an NHMRC Senior Research Fellow. G.T.B. is an Australian Research Council Future Fellow. A.K. is a fellow of the Sylvia and Charles Viertel Foundation. M.A.D.-E. is an NHMRC Principal Research Fellow. G.R.H. is an NHMRC Senior Principal Research Fellow and a Queensland Health Senior Clinical Research Fellow.

Publisher Copyright:
2017 © The Authors.

Publisher link

10.1126/sciimmunol.aah7152

http://europepmc.org/articles/pmc5714294

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Zhang, P., Lee, J. S., Gartlan, K. H., Schuster, I. S., Comerford, I., Varelias, A., Ullah, M. A., Vuckovic, S., Koyama, M., Kuns, R. D., Locke, K. R., Beckett, K. J., Olver, S. D., Samson, L. D., de Oca, M. M., Rivera, F. D. L., Clouston, A. D., Belz, G. T., Blazar, B. R., ... Hill, G. R. (2017). Eomesodermin promotes the development of type 1 regulatory T (T_R1) cells. Science Immunology, 2(10), Article eaah7152. https://doi.org/10.1126/sciimmunol.aah7152

Zhang, P, Lee, JS, Gartlan, KH, Schuster, IS, Comerford, I, Varelias, A, Ullah, MA, Vuckovic, S, Koyama, M, Kuns, RD, Locke, KR, Beckett, KJ, Olver, SD, Samson, LD, de Oca, MM, Rivera, FDL, Clouston, AD, Belz, GT, Blazar, BR, MacDonald, KP, McColl, SR, Thomas, R, Engwerda, CR, Degli-Esposti, MA, Kallies, A, Tey, SK & Hill, GR 2017, 'Eomesodermin promotes the development of type 1 regulatory T (T_R1) cells', Science Immunology, vol. 2, no. 10, eaah7152. https://doi.org/10.1126/sciimmunol.aah7152

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title = "Eomesodermin promotes the development of type 1 regulatory T (TR1) cells",

abstract = "Type 1 regulatory T (TR1) cells are Foxp3− interleukin-10 (IL-10)–producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.",

author = "Ping Zhang and Lee, {Jason S.} and Gartlan, {Kate H.} and Schuster, {Iona S.} and Iain Comerford and Antiopi Varelias and Ullah, {Md Ashik} and Slavica Vuckovic and Motoko Koyama and Kuns, {Rachel D.} and Locke, {Kelly R.} and Beckett, {Kirrilee J.} and Olver, {Stuart D.} and Samson, {Luke D.} and {de Oca}, {Marcela Montes} and Rivera, {Fabian de Labastida} and Clouston, {Andrew D.} and Belz, {Gabrielle T.} and Blazar, {Bruce R.} and MacDonald, {Kelli P.} and McColl, {Shaun R.} and Ranjeny Thomas and Engwerda, {Christian R.} and Degli-Esposti, {Mariapia A.} and Axel Kallies and Tey, {Siok Keen} and Hill, {Geoffrey R.}",

note = "Funding Information: We thank P. Hall, M. Rist, and G. Chojnowski for expert cell sorting and the animal facilities of QIMR Berghofer Medical Research Institute and M. Flynn for expert graphical work. This work was supported by research grants held by G.R.H. from the National Health and Medical Research Council (NHMRC; Australia). B.R.B. is supported by funds from the NIH (R01 AI34495, R01 HL56067, and AI 11879). C.R.E. is an NHMRC Senior Research Fellow. G.T.B. is an Australian Research Council Future Fellow. A.K. is a fellow of the Sylvia and Charles Viertel Foundation. M.A.D.-E. is an NHMRC Principal Research Fellow. G.R.H. is an NHMRC Senior Principal Research Fellow and a Queensland Health Senior Clinical Research Fellow. Publisher Copyright: 2017 {\textcopyright} The Authors.",

year = "2017",

doi = "10.1126/sciimmunol.aah7152",

language = "English (US)",

volume = "2",

journal = "Science Immunology",

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T1 - Eomesodermin promotes the development of type 1 regulatory T (TR1) cells

AU - Zhang, Ping

AU - Lee, Jason S.

AU - Gartlan, Kate H.

AU - Schuster, Iona S.

AU - Comerford, Iain

AU - Varelias, Antiopi

AU - Ullah, Md Ashik

AU - Vuckovic, Slavica

AU - Koyama, Motoko

AU - Kuns, Rachel D.

AU - Locke, Kelly R.

AU - Beckett, Kirrilee J.

AU - Olver, Stuart D.

AU - Samson, Luke D.

AU - de Oca, Marcela Montes

AU - Rivera, Fabian de Labastida

AU - Clouston, Andrew D.

AU - Belz, Gabrielle T.

AU - Blazar, Bruce R.

AU - MacDonald, Kelli P.

AU - McColl, Shaun R.

AU - Thomas, Ranjeny

AU - Engwerda, Christian R.

AU - Degli-Esposti, Mariapia A.

AU - Kallies, Axel

AU - Tey, Siok Keen

AU - Hill, Geoffrey R.

N1 - Funding Information: We thank P. Hall, M. Rist, and G. Chojnowski for expert cell sorting and the animal facilities of QIMR Berghofer Medical Research Institute and M. Flynn for expert graphical work. This work was supported by research grants held by G.R.H. from the National Health and Medical Research Council (NHMRC; Australia). B.R.B. is supported by funds from the NIH (R01 AI34495, R01 HL56067, and AI 11879). C.R.E. is an NHMRC Senior Research Fellow. G.T.B. is an Australian Research Council Future Fellow. A.K. is a fellow of the Sylvia and Charles Viertel Foundation. M.A.D.-E. is an NHMRC Principal Research Fellow. G.R.H. is an NHMRC Senior Principal Research Fellow and a Queensland Health Senior Clinical Research Fellow. Publisher Copyright: 2017 © The Authors.

PY - 2017

Y1 - 2017

N2 - Type 1 regulatory T (TR1) cells are Foxp3− interleukin-10 (IL-10)–producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.

AB - Type 1 regulatory T (TR1) cells are Foxp3− interleukin-10 (IL-10)–producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte–induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage–derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.

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