Sjögren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinase Academic Article uri icon

Overview

MeSH Major

  • Phosphatidylinositol 3-Kinases
  • Sjogren's Syndrome
  • T-Lymphocytes

abstract

  • Sjögren's syndrome (SS) is an autoimmune disease that is characterized by infiltration of exocrine tissues, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Here, we show that mice with T cell-specific loss of class IA phosphoinositide 3-kinase function develop organ-specific autoimmunity that resembles the human disease SS. Most mutant mice aged 3-8 months develop corneal opacity and eye lesions due to irritation and constant scratching. These mice display cardinal signs of primary SS such as marked lymphocytic infiltration of the lacrimal glands, antinuclear antibodies in the serum, and elevated titer of anti-SS-A antibody, in the absence of kidney pathology. Immunofluorescence studies show the presence of numerous CD4+ T cells with a smaller number of CD8+ T cells and B cells in the lacrimal glands. CD4+ T cells from these mice exhibit aberrant differentiation in vitro. These results indicate that aberrant T cells with impaired class IA phosphoinositide 3-kinase signaling can lead to organ-specific autoimmunity. In addition, the mouse model described here represents a tool to study the pathogenesis and treatment of SS.

publication date

  • November 7, 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1636548

Digital Object Identifier (DOI)

  • 10.1073/pnas.0607984103

PubMed ID

  • 17071741

Additional Document Info

start page

  • 16882

end page

  • 7

volume

  • 103

number

  • 45