Differentially expressed genes in MHC-compatible rat strains that are susceptible or resistant to experimental autoimmune uveitis
Mary J Mattapallil 1,
Andrea Augello 2,
Chris Cheadle 3,
Diane Teichberg 3,
Kevin Becker 3,
Chi-Chao Chan 1,
Joseph J Mattapallil 4,
Giuseppina Pennesi 5,
and
Rachel R. Caspi 6*
1 NEI, LI, NIH, Bethesda, Maryland, United States
2 Dept Oncol, N
U. Genova, Genova, Italy
3 NIA, Array Unit, NIH, Baltimore, Maryland, United States
4 Dept Microbiol & Immunol, USUHS, Bethesda, Maryland, United States
5 Dept Oncol, U Genova, Genova, Italy
6 Laboratory of Immunology, NEI - NIH, Building 10, Room 10N222, Bethesda, Maryland, 20892-1857, United States
* To whom correspondence should be addressed. E-mail: rcaspi{at}helix.nih.gov.
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Abstract |
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PURPOSE: Experimental autoimmune uveitis (EAU) is an established model for immune-mediated human uveitis. Though a number of genes from MHC loci have been shown to play a role in uveitis, little is known about the role of non-MHC genes in the pathogenesis of EAU. Several non-MHC genes have been implicated in the pathogenesis of various autoimmune diseases. The primary objective of this study was to identify the non-MHC genes involved in the pathogenesis of EAU to identify potential drug targets and to possibly target their protein products for immunotherapy.
METHODS: EAU was induced in the susceptible (Lewis; LEW) or resistant (Fischer 344; F344) rats that have identical MHC class II haplotype. Draining lymph node cells were obtained during the innate and adaptive phase of the immune response and the pattern of gene expression was evaluated using microarray technology. Differentially expressed genes were validated at mRNA and protein levels using various methods.
RESULTS: Susceptibility to EAU was associated with an increased expression of numerous non-MHC genes such as Th1-type cytokines/chemokines, anti-apoptotic factors, hormones and neurotransmitters, and a downregulation of selected adhesion molecules. Using a combined genetic-genomic approach we have identified different patterns of gene expression associated with the sensitization and effector phase of EAU pathogenesis.
CONCLUSION: Our data demonstrate that the differential expression of several non-MHC genes is associated with the mechanism of uveitis.
Key Words:
autoimmune response/disease, gene expression, uveitis, cytokine
