Tubular antigen-binding proteins repress transcription of type IV collagen in the autoimmune target epithelium of experimental interstitial nephritis

Thomas P. Haverty, Carolyn J. Kelly, John R. Hoyer, Rene Alvarez, Eric G. Neilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)517-523
Number of pages7
JournalJournal of Clinical Investigation
Volume89
Issue number2
DOIs
StatePublished - 1992

Keywords

  • Autoimmune tubular atrophy
  • Basement membranes
  • Renal epithelium
  • T cells

ASJC Scopus subject areas

  • Medicine(all)

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