Blockade of lymphotoxin signaling inhibits the clinical expression of murine graft-versus-host skin disease.
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 LTbeta receptor-Ig fusion protein (LTbetaR-Ig). The recipient mice treated with control human Ig developed clinically apparent, severe skin lesions. However, none of the mice treated with LTbetaR-Ig developed clinical skin disease. The expression of ICAM-1 in cutaneous tissue was also much lower in mice treated with LTbetaR-Ig than in mice treated with human Ig. Thus, the inhibition of LT signaling via LTbetaR-Ig treatment appears to be capable of markedly ameliorating the development of GVHSD, possibly by inhibiting the expression of adhesion molecules.
Wu
Qiang
Q
Department of Dermatology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Fu
Yang-Xin
YX
Sontheimer
Richard D
RD
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D017209:Apoptosis / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015431:Weight Loss / Q000276:immunology
D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; C505886:LTB protein, human; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens