Tubular antigen-binding proteins repress transcription of type IV collagen in the autoimmune target epithelium of experimental interstitial nephritis.
We have been studying immune interactions with somatic cells using a tubular antigen-binding protein (ThF) secreted by helper T lymphocytes harvested from mice that have an autoimmune form of interstitial nephritis called anti-tubular basement membrane disease. This ThF, although characterized originally because of its ability to induce effector T cells, additionally recognizes the nephritogenic 3M-1 antigen expressed by its target renal tubular epithelium. We believe these proteins, in general, may modulate directly some homeostatic functions in organ-derived cells, and now report that our ThF represses specifically the cellular transcription and secretion of basement membrane type IV collagen in tubular epithelium. These in vitro findings of reduced levels of mRNA encoding type IV collagen correlate well with in situ hybridization studies performed on kidneys expressing early autoimmune lesions, and predict a progressive drop in the expression of type IV collagen in the interstitium. Such a novel and unexpected repression of transcription of type IV collagen might easily impart or facilitate permanent change in the infrastructure of kidney architecture during autoimmune injury and, perhaps, contributes to the process of tubular atrophy attendant to prolonged renal inflammation.
Haverty
T P
TP
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6144.
Kelly
C J
CJ
Hoyer
J R
JR
Alvarez
R
R
Neilson
E G
EG
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D001485:Basement Membrane / Q000276:immunology; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D007114:Immunization; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000276:immunology*; D051379:Mice; D009395:Nephritis, Interstitial / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D003094:Collagen