TIM-1 Glycoprotein Binds the Adhesion Receptor P-Selectin and Mediates T Cell Trafficking during Inflammation and Autoimmunity

被引：90

作者：

Angiari, Stefano ^{[1
]}

Donnarumma, Tiziano ^{[1
]}

Rossi, Barbara ^{[1
]}

Dusi, Silvia ^{[1
]}

Pietronigro, Enrica ^{[1
]}

Zenaro, Elena ^{[1
]}

Della Bianca, Vittorina ^{[1
]}

Toffali, Lara ^{[1
,4
]}

Piacentino, Gennj ^{[1
]}

Budui, Simona ^{[1
]}

Rennert, Paul ^{[2
]}

Xiao, Sheng ^{[3
]}

Laudanna, Carlo ^{[1
,4
]}

Casasnovas, Jose M. ^{[5
]}

Kuchroo, Vijay K. ^{[3
]}

Constantin, Gabriela ^{[1
]}

机构：

[1] Univ Verona, Dept Pathol & Diagnost, Sect Gen Pathol, Str Le Grazie 8, I-37134 Verona, Italy

[2] Biogen Idec Inc, Dept Mol Discovery & Immunobiol, Brookline, MA 02146 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[4] Univ Verona, Ctr Biomed Comp CBMC, I-37134 Verona, Italy

[5] CNB CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain

来源：

IMMUNITY | 2014年 / 40卷 / 04期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

CENTRAL-NERVOUS-SYSTEM; RECRUITMENT; RECOGNITION; MECHANISMS; ROLES; ACTIVATION; IMMUNITY; FAMILY; LIGAND; SITE;

D O I：

10.1016/j.immuni.2014.03.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper 1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but it reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 immunoglobulin variable domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease.

引用

页码：542 / 553

页数：12

共 29 条

[1]

P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues [J].