Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells

Zhang, Ping, Lee, Jason S., Gartlan, Kate H., Schuster, Iona S., Comerford, Iain, Varelias, Antiopi, Ullah, Md Ashik, Vuckovic, Slavica, Koyama, Motoko, Kuns, Rachel D., Locke, Kelly R., Beckett, Kirrilee J., Olver, Stuart D., Samson, Luke D., Montes de Oca, Marcela, de Labastida Rivera, Fabian, Clouston, Andrew D., Belz, Gabrielle T., Blazar, Bruce R., MacDonald, Kelli P., McColl, Shaun R., Thomas, Ranjeny, Engwerda, Christian R., Degli-Esposti, Mariapia A., Kallies, Axel, Tey, Siok-Keen and Hill, Geoffrey R. (2017) Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells. Science Immunology, 2 10: . doi:10.1126/sciimmunol.aah7152


Author Zhang, Ping
Lee, Jason S.
Gartlan, Kate H.
Schuster, Iona S.
Comerford, Iain
Varelias, Antiopi
Ullah, Md Ashik
Vuckovic, Slavica
Koyama, Motoko
Kuns, Rachel D.
Locke, Kelly R.
Beckett, Kirrilee J.
Olver, Stuart D.
Samson, Luke D.
Montes de Oca, Marcela
de Labastida Rivera, Fabian
Clouston, Andrew D.
Belz, Gabrielle T.
Blazar, Bruce R.
MacDonald, Kelli P.
McColl, Shaun R.
Thomas, Ranjeny
Engwerda, Christian R.
Degli-Esposti, Mariapia A.
Kallies, Axel
Tey, Siok-Keen
Hill, Geoffrey R.
Title Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells
Formatted title
Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells
Journal name Science Immunology   Check publisher's open access policy
ISSN 2470-9468
Publication date 2017-04-07
Sub-type Article (original research)
DOI 10.1126/sciimmunol.aah7152
Open Access Status Not yet assessed
Volume 2
Issue 10
Total pages 1
Place of publication Washington, DC, United States
Publisher American Association for the Advancement of Science
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.
Formatted 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.
Keyword Allogeneic bone marrow transplantation (BMT)
Eomesodermin
Eomes
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 AI034495
R01 HL056067
R01 HL118979
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
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Created: Thu, 08 Jun 2017, 08:45:21 EST by Professor Ranjeny Thomas on behalf of UQ Diamantina Institute