The role of Fas-Fas ligand-mediated apoptosis in autoimmune lacrimal gland disease in MRL/MpJ mice

D. A. Jabs, B. Lee, J. Whittum-Hudson, R. A. Prendergast

Research output: Contribution to journalArticle

Abstract

Purpose. MRL/MpJ mice spontaneously develop lacrimal gland inflammation and are a model for the human disorder Sjögren's syndrome. MRL/MpJ-lpr/lpr (MRL/lpr) and MRL/Mp-+/+ (MRL/+) mice are congenic substrains, which differ only by a single autosomal recessive gene, the lpr mutation. This mutation results in defective Fas protein, defective lymphocytic apoptosis, and accelerated autoimmune lacrimal gland disease in MRL/Ipr mice. We evaluated apoptosis in the lacrimal glands of MRL/lpr and MRL/+ mice. Methods. Inflammatory cells in the lacrimal glands of MRL/Ipr and MRL/+ mice were evaluated for apoptosis with TUNEL staining and Fas and Fas ligand expression with immunohistochemistry. Results. MRL/lpr mice had a greater percentage of the lacrimal gland replaced by inflammatory infiltrate (30.3% ± 7.0%) than did MRL/+ mice (13.0% ± 3.0%, P = 0.02). However, similar amounts of lymphocytic apoptosis were present in the lacrimal glands of MRL/lpr and MRL/+ mice. The mean number of apoptotic cells per unit area of inflammation was 23.8 ± 2.4 in MRL/lpr mice and 24.6 ± 6.0 in MRL/+ mice (P = 0.91). Fas expression was absent on lymphocytes in MRL/lpr mice but was present on lymphocytes in MRL/+ mice. Fas ligand expression was present on epithelial structures in both substrains. Conclusions. The accelerated lacrimal gland disease inflammation in MRL/lpr mice does not appear to be due to decreased apoptosis in the microenvironment of the lacrimal gland of MRL/lpr mice. It appears that in MRL/lpr mice there is defective extrathymic lymphoid apoptosis, permitting a relatively greater expansion of autoreactive T cells, which subsequently invade the lacrimal gland.

Original languageEnglish (US)
Pages (from-to)399-401
Number of pages3
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'The role of Fas-Fas ligand-mediated apoptosis in autoimmune lacrimal gland disease in MRL/MpJ mice'. Together they form a unique fingerprint.

  • Cite this