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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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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 -