Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease
Copyright policy )Blockade of Lymphotoxin Signaling Inhibits the Clinical Expression of Murine Graft-versus-Host Skin Disease
AbstractAdhesion 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.
- University of Chicago United States
- Roy J. and Lucille A. Carver College of Medicine United States
- University of Iowa Health Care United States
- University of Iowa United States
Keratinocytes, Lymphotoxin-beta, Graft vs Host Disease, Membrane Proteins, Apoptosis, Skin Diseases, Mice, Inbred C57BL, Minor Histocompatibility Antigens, Mice, Cell Movement, Cell Migration Inhibition, Animals, Humans, Female, Epidermis, Antibodies, Blocking, Cell Adhesion Molecules, Lymphotoxin-alpha, Bone Marrow Transplantation, Signal Transduction
Keratinocytes, Lymphotoxin-beta, Graft vs Host Disease, Membrane Proteins, Apoptosis, Skin Diseases, Mice, Inbred C57BL, Minor Histocompatibility Antigens, Mice, Cell Movement, Cell Migration Inhibition, Animals, Humans, Female, Epidermis, Antibodies, Blocking, Cell Adhesion Molecules, Lymphotoxin-alpha, Bone Marrow Transplantation, Signal Transduction
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