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

Izabela Komarowska; David Coe; Guosu Wang; Robert Haas; Claudio Mauro; Madhav Kishore; Dianne Cooper; Suchita Nadkarni; Hongmei Fu; Daniel a. Steinbruchel; Costantino Pitzalis; Graham Anderson; Pat Bucy; Giovanna Lombardi; Ross Breckenridge; Federica m. Marelli-berg

doi:10.1016/j.immuni.2015.05.014

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

Izabela Komarowska, David Coe, Guosu Wang, Robert Haas, Claudio Mauro, Madhav Kishore, Dianne Cooper, Suchita Nadkarni, Hongmei Fu, Daniel a. Steinbruchel, Costantino Pitzalis, Graham Anderson, Pat Bucy, Giovanna Lombardi, Ross Breckenridge, Federica m. Marelli-berg

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

172 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	1087-1099
Number of pages	13
Journal	Immunity
Volume	42
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2015.05.014 https://doi.org/10.1016/j.immuni.2015.05.014
Publication status	Published - 16 Jun 2015

Bibliographical note

Keywords

Animals
Autocrine Communication
Cell Movement
Cells, Cultured
Graft Rejection
Heart
Heart Transplantation
Hepatocyte Growth Factor
Humans
Immunologic Memory
Indoles
Lymphocyte Activation
Mice
Mice, SCID
Molecular Targeted Therapy
Proto-Oncogene Proteins c-met
RNA, Small Interfering
Receptors, CCR5
Receptors, Chemokine
Receptors, Lymphocyte Homing
Signal Transduction
Sulfones
T-Lymphocytes

Access to Document

1-s2.0-S1074761315002125-mainFinal published version, 4.87 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

http://linkinghub.elsevier.com/retrieve/pii/S1074761315002125

Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G., Jenkinson, E. & Lane, P.
Medical Research Council
1/10/10 → 30/09/15
Project: Research Councils

Cite this

Komarowska, I., Coe, D., Wang, G., Haas, R., Mauro, C., Kishore, M., Cooper, D., Nadkarni, S., Fu, H., Steinbruchel, D., Pitzalis, C., Anderson, G., Bucy, P., Lombardi, G., Breckenridge, R., & Marelli-berg, F. (2015). Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release. Immunity, 42(6), 1087-1099. https://doi.org/10.1016/j.immuni.2015.05.014, https://doi.org/10.1016/j.immuni.2015.05.014

@article{5fb79efbed814419bf5c14e3affea461,

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

abstract = "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.",

keywords = "Animals, Autocrine Communication, Cell Movement, Cells, Cultured, Graft Rejection, Heart, Heart Transplantation, Hepatocyte Growth Factor, Humans, Immunologic Memory, Indoles, Lymphocyte Activation, Mice, Mice, SCID, Molecular Targeted Therapy, Proto-Oncogene Proteins c-met, RNA, Small Interfering, Receptors, CCR5, Receptors, Chemokine, Receptors, Lymphocyte Homing, Signal Transduction, Sulfones, T-Lymphocytes",

author = "Izabela Komarowska and David Coe and Guosu Wang and Robert Haas and Claudio Mauro and Madhav Kishore and Dianne Cooper and Suchita Nadkarni and Hongmei Fu and Daniel a. Steinbruchel and Costantino Pitzalis and Graham Anderson and Pat Bucy and Giovanna Lombardi and Ross Breckenridge and Federica m. Marelli-berg",

year = "2015",

month = jun,

day = "16",

doi = "10.1016/j.immuni.2015.05.014",

language = "English",

volume = "42",

pages = "1087--1099",

journal = "Immunity",

issn = "1074-7613",

publisher = "Elsevier",

number = "6",

}

Komarowska, I, Coe, D, Wang, G, Haas, R, Mauro, C, Kishore, M, Cooper, D, Nadkarni, S, Fu, H, Steinbruchel, D, Pitzalis, C, Anderson, G, Bucy, P, Lombardi, G, Breckenridge, R & Marelli-berg, F 2015, 'Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release', Immunity, vol. 42, no. 6, pp. 1087-1099. https://doi.org/10.1016/j.immuni.2015.05.014, https://doi.org/10.1016/j.immuni.2015.05.014

TY - JOUR

T1 - Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release

AU - Komarowska, Izabela

AU - Coe, David

AU - Wang, Guosu

AU - Haas, Robert

AU - Mauro, Claudio

AU - Kishore, Madhav

AU - Cooper, Dianne

AU - Nadkarni, Suchita

AU - Fu, Hongmei

AU - Steinbruchel, Daniel a.

AU - Pitzalis, Costantino

AU - Anderson, Graham

AU - Bucy, Pat

AU - Lombardi, Giovanna

AU - Breckenridge, Ross

AU - Marelli-berg, Federica m.

PY - 2015/6/16

Y1 - 2015/6/16

N2 - 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.

AB - 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.

KW - Animals

KW - Autocrine Communication

KW - Cell Movement

KW - Cells, Cultured

KW - Graft Rejection

KW - Heart

KW - Heart Transplantation

KW - Hepatocyte Growth Factor

KW - Humans

KW - Immunologic Memory

KW - Indoles

KW - Lymphocyte Activation

KW - Mice

KW - Mice, SCID

KW - Molecular Targeted Therapy

KW - Proto-Oncogene Proteins c-met

KW - RNA, Small Interfering

KW - Receptors, CCR5

KW - Receptors, Chemokine

KW - Receptors, Lymphocyte Homing

KW - Signal Transduction

KW - Sulfones

KW - T-Lymphocytes

U2 - 10.1016/j.immuni.2015.05.014

DO - 10.1016/j.immuni.2015.05.014

M3 - Article

C2 - 26070483

SN - 1074-7613

VL - 42

SP - 1087

EP - 1099

JO - Immunity

JF - Immunity

IS - 6

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Projects

Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance

Cite this