Sjögren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinase.
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.
Oak
Jean S
JS
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Deane
Jonathan A
JA
Kharas
Michael G
MG
Luo
Ji
J
Lane
Thomas E
TE
Cantley
Lewis C
LC
Fruman
David A
DA
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007765:Lacrimal Apparatus / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000145:classification / Q000172:deficiency*; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D019869:Phosphatidylinositol 3-Kinases