Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease

Qiang Wu, Yang Xin Fu, Richard D. Sontheimer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Adhesion molecules are essential for the recruitment of T cells into the skin during the development of graft-vs-host skin disease (GVHSD). However, the mechanisms responsible for the regulation of expression of cutaneous adhesion molecules in this setting are still poorly understood. In this study we blocked lymphotoxin (LT) signaling in a murine model of minor histocompatibility Ag system mismatch GVHSD by using an LTβ receptor-Ig fusion protein (LTβR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTβR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTβR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTβR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.

Original languageEnglish (US)
Pages (from-to)1630-1636
Number of pages7
JournalJournal of Immunology
Volume172
Issue number3
StatePublished - Feb 1 2004

Fingerprint

Lymphotoxin-alpha
Graft vs Host Disease
Skin Diseases
Skin
Proteins
Histocompatibility
Intercellular Adhesion Molecule-1
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease. / Wu, Qiang; Fu, Yang Xin; Sontheimer, Richard D.

In: Journal of Immunology, Vol. 172, No. 3, 01.02.2004, p. 1630-1636.

Research output: Contribution to journalArticle

@article{69e73edd6a8949d3b8840998471cf03b,
title = "Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease",
abstract = "Adhesion molecules are essential for the recruitment of T cells into the skin during the development of graft-vs-host skin disease (GVHSD). However, the mechanisms responsible for the regulation of expression of cutaneous adhesion molecules in this setting are still poorly understood. In this study we blocked lymphotoxin (LT) signaling in a murine model of minor histocompatibility Ag system mismatch GVHSD by using an LTβ receptor-Ig fusion protein (LTβR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTβR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTβR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTβR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.",
author = "Qiang Wu and Fu, {Yang Xin} and Sontheimer, {Richard D.}",
year = "2004",
month = "2",
day = "1",
language = "English (US)",
volume = "172",
pages = "1630--1636",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease

AU - Wu, Qiang

AU - Fu, Yang Xin

AU - Sontheimer, Richard D.

PY - 2004/2/1

Y1 - 2004/2/1

N2 - Adhesion molecules are essential for the recruitment of T cells into the skin during the development of graft-vs-host skin disease (GVHSD). However, the mechanisms responsible for the regulation of expression of cutaneous adhesion molecules in this setting are still poorly understood. In this study we blocked lymphotoxin (LT) signaling in a murine model of minor histocompatibility Ag system mismatch GVHSD by using an LTβ receptor-Ig fusion protein (LTβR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTβR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTβR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTβR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.

AB - Adhesion molecules are essential for the recruitment of T cells into the skin during the development of graft-vs-host skin disease (GVHSD). However, the mechanisms responsible for the regulation of expression of cutaneous adhesion molecules in this setting are still poorly understood. In this study we blocked lymphotoxin (LT) signaling in a murine model of minor histocompatibility Ag system mismatch GVHSD by using an LTβ receptor-Ig fusion protein (LTβR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTβR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTβR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTβR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.

UR - http://www.scopus.com/inward/record.url?scp=1642444092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642444092&partnerID=8YFLogxK

M3 - Article

C2 - 14734744

AN - SCOPUS:1642444092

VL - 172

SP - 1630

EP - 1636

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -