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Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation

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Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation. / Worthington, John J.; Kelly, Aoife; Smedley, Catherine; Bauché, David; Campbell, Simon; Marie, Julien C.; Travis, Mark A.

In: Immunity, Vol. 42, No. 5, 19.05.2015, p. 903-915.

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Worthington, John J. ; Kelly, Aoife ; Smedley, Catherine ; Bauché, David ; Campbell, Simon ; Marie, Julien C. ; Travis, Mark A. / Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation. In: Immunity. 2015 ; Vol. 42, No. 5. pp. 903-915.

Bibtex

@article{5396384501df459e8ba2db7fb795b4d3,
title = "Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation",
abstract = "Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.",
keywords = "Animals, Cell Proliferation, Colitis, Disease Models, Animal, Gene Expression Regulation, Humans, Inflammation, Inflammation Mediators, Integrins, Mice, Models, Immunological, T-Lymphocytes, Regulatory, Transforming Growth Factor beta",
author = "Worthington, {John J.} and Aoife Kelly and Catherine Smedley and David Bauch{\'e} and Simon Campbell and Marie, {Julien C.} and Travis, {Mark A.}",
note = "This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).",
year = "2015",
month = may
day = "19",
doi = "10.1016/j.immuni.2015.04.012",
language = "English",
volume = "42",
pages = "903--915",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Integrin αvβ8-mediated TGF-β activation by effector regulatory T sells is essential for suppression of T-Cell-mediated inflammation

AU - Worthington, John J.

AU - Kelly, Aoife

AU - Smedley, Catherine

AU - Bauché, David

AU - Campbell, Simon

AU - Marie, Julien C.

AU - Travis, Mark A.

N1 - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PY - 2015/5/19

Y1 - 2015/5/19

N2 - Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.

AB - Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.

KW - Animals

KW - Cell Proliferation

KW - Colitis

KW - Disease Models, Animal

KW - Gene Expression Regulation

KW - Humans

KW - Inflammation

KW - Inflammation Mediators

KW - Integrins

KW - Mice

KW - Models, Immunological

KW - T-Lymphocytes, Regulatory

KW - Transforming Growth Factor beta

U2 - 10.1016/j.immuni.2015.04.012

DO - 10.1016/j.immuni.2015.04.012

M3 - Journal article

C2 - 25979421

VL - 42

SP - 903

EP - 915

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 5

ER -