TY - JOUR
T1 - Differentially expressed genes in MHC-compatible rat strains that are susceptible or resistant to experimental autoimmune uveitis
AU - Mattapallil, Mary J.
AU - Augello, Andrea
AU - Cheadle, Chris
AU - Teichberg, Diane
AU - Becker, Kevin G.
AU - Chan, Chi Chao
AU - Mattapallil, Joseph J.
AU - Pennesi, Giuseppina
AU - Caspi, Rachel R.
PY - 2008/4
Y1 - 2008/4
N2 - Purpose. Experimental autoimmune uveitis (EAU) is an established model for immune-mediated human uveitis. Although several genes from major histocompatibility complex (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 pathogen- esis 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 possibly to 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 and chemokines, antiapoptotic factors, hormones, and neurotransmitters and a downregulation of selected adhesion molecules. In this study a combined genetic-genomic approach was used to identify different patterns of gene expression associated with the sensitization and effector phase of EAU pathogenesis.Conclusions. The data demonstrate that the differential expression of several non-MHC genes is associated with the mechanism of uveitis.
AB - Purpose. Experimental autoimmune uveitis (EAU) is an established model for immune-mediated human uveitis. Although several genes from major histocompatibility complex (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 pathogen- esis 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 possibly to 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 and chemokines, antiapoptotic factors, hormones, and neurotransmitters and a downregulation of selected adhesion molecules. In this study a combined genetic-genomic approach was used to identify different patterns of gene expression associated with the sensitization and effector phase of EAU pathogenesis.Conclusions. The data demonstrate that the differential expression of several non-MHC genes is associated with the mechanism of uveitis.
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U2 - 10.1167/iovs.07-1295
DO - 10.1167/iovs.07-1295
M3 - Article
C2 - 18281616
AN - SCOPUS:44649094799
SN - 0146-0404
VL - 49
SP - 1957
EP - 1970
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 5
ER -