Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

被引：56
作者：
Brinkman, C. Colin [1 ,2 ,3 ]
Iwami, Daiki [1 ,3 ,5 ]
Hritzo, Molly K. [2 ]
Xiong, Yanbao [1 ,2 ,3 ]
Ahmad, Sarwat [1 ,3 ]
Simon, Thomas [1 ,2 ,3 ]
Hippen, Keli L. [4 ]
Blazar, Bruce R. [4 ]
Bromberg, Jonathan S. [1 ,2 ,3 ]
机构：
[1] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA
[4] Univ Minnesota, Ctr Canc, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA
[5] Hokkaido Univ, Dept Renal & Genito Urinary Surg, Kita Ku, Kita 15,Nishi 7, Sapporo, Hokkaido 0608638, Japan
来源：
NATURE COMMUNICATIONS | 2016年 / 7卷
关键词：
REGULATORY T-CELLS; HIGH ENDOTHELIAL VENULES; B-INDUCING KINASE; GENE-EXPRESSION; LEUKOCYTE TRANSMIGRATION; AUTOIMMUNE-DISEASE; PERIPHERAL-TISSUES; VESSEL ENDOTHELIUM; DENDRITIC CELLS; DEFICIENT MICE;
D O I：
10.1038/ncomms12021
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 LT alpha beta rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NF kappa B signalling via LT beta R. 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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页数：16
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