Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery

Michael J. Barnes, Philippe Krebs, Nathaniel Harris, Celine Eidenschenk, Rosana Gonzalez-Quintial, Carrie N. Arnold, Karine Crozat, Sosathya Sovath, Eva Marie Moresco, Argyrios N. Theofilopoulos, Bruce Beutler, Kasper Hoebe

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Regulatory T (Treg) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4+ T cells in a cytokine dependent manner. T reg cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4+Foxp3+ Treg cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient Treg cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFβ) and interleukin-2 (IL-2). In vivo, a small peripheral T reg pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral Treg cells are a dynamic population that may expand to limit immunopathology or promote chronic infection. Copyright:

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalPLoS Biology
Volume7
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Thymus
T-cells
Cell Lineage
Regulatory T-Lymphocytes
Thymus Gland
T-lymphocytes
Cytokines
Population dynamics
T-Cell Antigen Receptor
Transforming Growth Factor beta
Interleukin-2
Cells
cells
Murid herpesvirus 1
transforming growth factor beta 2
cytokines
immunopathology
thymocytes
Muromegalovirus
mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Barnes, M. J., Krebs, P., Harris, N., Eidenschenk, C., Gonzalez-Quintial, R., Arnold, C. N., ... Hoebe, K. (2009). Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery. PLoS Biology, 7(3), 513-524. https://doi.org/10.1371/journal.pbio.1000051

Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery. / Barnes, Michael J.; Krebs, Philippe; Harris, Nathaniel; Eidenschenk, Celine; Gonzalez-Quintial, Rosana; Arnold, Carrie N.; Crozat, Karine; Sovath, Sosathya; Moresco, Eva Marie; Theofilopoulos, Argyrios N.; Beutler, Bruce; Hoebe, Kasper.

In: PLoS Biology, Vol. 7, No. 3, 03.2009, p. 513-524.

Research output: Contribution to journalArticle

Barnes, MJ, Krebs, P, Harris, N, Eidenschenk, C, Gonzalez-Quintial, R, Arnold, CN, Crozat, K, Sovath, S, Moresco, EM, Theofilopoulos, AN, Beutler, B & Hoebe, K 2009, 'Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery', PLoS Biology, vol. 7, no. 3, pp. 513-524. https://doi.org/10.1371/journal.pbio.1000051
Barnes MJ, Krebs P, Harris N, Eidenschenk C, Gonzalez-Quintial R, Arnold CN et al. Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery. PLoS Biology. 2009 Mar;7(3):513-524. https://doi.org/10.1371/journal.pbio.1000051
Barnes, Michael J. ; Krebs, Philippe ; Harris, Nathaniel ; Eidenschenk, Celine ; Gonzalez-Quintial, Rosana ; Arnold, Carrie N. ; Crozat, Karine ; Sovath, Sosathya ; Moresco, Eva Marie ; Theofilopoulos, Argyrios N. ; Beutler, Bruce ; Hoebe, Kasper. / Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery. In: PLoS Biology. 2009 ; Vol. 7, No. 3. pp. 513-524.
@article{3559486ac51a46de812eeea4083c4c0a,
title = "Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery",
abstract = "Regulatory T (Treg) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4+ T cells in a cytokine dependent manner. T reg cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4+Foxp3+ Treg cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient Treg cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFβ) and interleukin-2 (IL-2). In vivo, a small peripheral T reg pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral Treg cells are a dynamic population that may expand to limit immunopathology or promote chronic infection. Copyright:",
author = "Barnes, {Michael J.} and Philippe Krebs and Nathaniel Harris and Celine Eidenschenk and Rosana Gonzalez-Quintial and Arnold, {Carrie N.} and Karine Crozat and Sosathya Sovath and Moresco, {Eva Marie} and Theofilopoulos, {Argyrios N.} and Bruce Beutler and Kasper Hoebe",
year = "2009",
month = "3",
doi = "10.1371/journal.pbio.1000051",
language = "English (US)",
volume = "7",
pages = "513--524",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Commitment to the regulatory t cell lineage requires CARMA1 in the thymus but not in the periphery

AU - Barnes, Michael J.

AU - Krebs, Philippe

AU - Harris, Nathaniel

AU - Eidenschenk, Celine

AU - Gonzalez-Quintial, Rosana

AU - Arnold, Carrie N.

AU - Crozat, Karine

AU - Sovath, Sosathya

AU - Moresco, Eva Marie

AU - Theofilopoulos, Argyrios N.

AU - Beutler, Bruce

AU - Hoebe, Kasper

PY - 2009/3

Y1 - 2009/3

N2 - Regulatory T (Treg) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4+ T cells in a cytokine dependent manner. T reg cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4+Foxp3+ Treg cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient Treg cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFβ) and interleukin-2 (IL-2). In vivo, a small peripheral T reg pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral Treg cells are a dynamic population that may expand to limit immunopathology or promote chronic infection. Copyright:

AB - Regulatory T (Treg) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4+ T cells in a cytokine dependent manner. T reg cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4+Foxp3+ Treg cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient Treg cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFβ) and interleukin-2 (IL-2). In vivo, a small peripheral T reg pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral Treg cells are a dynamic population that may expand to limit immunopathology or promote chronic infection. Copyright:

UR - http://www.scopus.com/inward/record.url?scp=65549114796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549114796&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1000051

DO - 10.1371/journal.pbio.1000051

M3 - Article

VL - 7

SP - 513

EP - 524

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 3

ER -