Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

C. Colin Brinkman; Daiki Iwami; Molly K. Hritzo; Yanbao Xiong; Sarwat Ahmad; Thomas Simon; Keli L. Hippen; Bruce R. Blazar; Jonathan S. Bromberg

doi:10.1038/ncomms12021

Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

C. Colin Brinkman, Daiki Iwami, Molly K. Hritzo, Yanbao Xiong, Sarwat Ahmad, Thomas Simon, Keli L. Hippen, Bruce R. Blazar, Jonathan S. Bromberg

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56 Scopus citations

Abstract

Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NF° B signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.

Original language	English (US)
Article number	12021
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12021
State	Published - Jun 21 2016

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abstract = "Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NF° B signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.",

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AU - Brinkman, C. Colin

AU - Iwami, Daiki

AU - Hritzo, Molly K.

AU - Xiong, Yanbao

AU - Ahmad, Sarwat

AU - Simon, Thomas

AU - Hippen, Keli L.

AU - Blazar, Bruce R.

AU - Bromberg, Jonathan S.

PY - 2016/6/21

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AB - Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NF° B signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.

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Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

Abstract

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