Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice.
Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the occurrence of autoantibodies characteristic for scleroderma. In order to study the role of autoimmunity in the production of skin fibrosis, we conducted adoptive transfer experiments in which bone marrow cells of TSK/pa mice were infused into pa/pa mice littermates. (C57BL/6 pa/pa mice are used to produce heterozygous TSK/pa mice). Our results showed that after a prodromal period of several months, the transfer of bone marrow cells led to skin fibrosis, the presence of autoantibodies, and increased transcription of (alpha 1) collagen I and TGF beta genes. Infusion of enriched B or T cells alone did not cause skin fibrosis but of B cells alone increased autoantibody production. By contrast, transfer of T and B lymphocytes led to earlier mild fibrosis, cellular infiltration and autoantibody production as well as increased transcription of the (alpha 1) collagen gene. Our results strongly demonstrate, for the first time, that immunocompetent cells can play a role in the activation of collagen synthesis leading to skin fibrosis.
Phelps
R G
RG
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574.
Daian
C
C
Shibata
S
S
Fleischmajer
R
R
Bona
C A
CA
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D003240:Connective Tissue Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D006965:Hyperplasia; D007121:Immunocompetence; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008211:Lymphocyte Cooperation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000276:immunology*; D012595:Scleroderma, Systemic; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen