Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

被引：81

作者：

Komarowska, Izabela ^{[1
]}

Coe, David ^{[1
]}

Wang, Guosu ^{[1
]}

Haas, Robert ^{[1
]}

Mauro, Claudio ^{[1
]}

Kishore, Madhav ^{[1
]}

Cooper, Dianne ^{[1
]}

Nadkarni, Suchita ^{[1
]}

Fu, Hongmei ^{[1
]}

Steinbruchel, Daniel A. ^{[2
]}

Pitzalis, Costantino ^{[1
]}

Anderson, Graham ^{[3
]}

Bucy, Pat ^{[4
]}

Lombardi, Giovanna ^{[5
]}

Breckenridge, Ross ^{[6
]}

Marelli-Berg, Federica M. ^{[1
]}

机构：

[1] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England

[2] Copenhagen Univ Hosp, Dept Thorac Surg, DK-2100 Copenhagen, Denmark

[3] Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England

[4] Univ Alabama Birmingham, Birmingham, AL 35233 USA

[5] Kings Coll London, MRC, Ctr Transplantat, London SE1 1UL, England

[6] UCL, Div Med, BHF Labs, London WC1E 6JJ, England

来源：

IMMUNITY | 2015年 / 42卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

DENDRITIC CELLS; IN-VIVO; REJECTION; LYMPHOCYTES; ACTIVATION; EXPRESSION; MODEL; MICE; REGENERATION; RECRUITMENT;

D O I：

10.1016/j.immuni.2015.05.014

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing'' receptors acquired by memory T cells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs T cell cardiotropism, which was associated with a specialized homing "`signature'' (c-Met(+)CCR4(+)CXCR3(+)). c-Met signals facilitated T cell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic T cell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during T cell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive T cells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.

引用

页码：1087 / 1099

页数：13

共 34 条

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