title: Comparative antigen-induced gene expression profiles unveil novel aspects of susceptibility/resistance to adjuvant arthritis in rats.
abstract: Lewis (LEW) and Wistar Kyoto (WKY) rats of the same major histocompatibility complex (MHC) haplotype (RT.1(l)) display differential susceptibility to adjuvant-induced arthritis (AIA). LEW are susceptible while WKY are resistant to AIA. To gain insights into the mechanistic basis of these disparate outcomes, we compared the gene expression profiles of the draining lymph node cells (LNC) of these two rat strains early (day 7) following a potentially arthritogenic challenge. LNC were tested both ex vivo and after restimulation with the disease-related antigen, mycobacterial heat-shock protein 65. Biotin-labeled fragment cRNA was generated from RNA of LNC and then hybridized with an oligonucleotide-based DNA microarray chip. The differentially expressed genes (DEG) were compared by limiting the false discovery rate to <5% and fold change ≥2.0, and their association with quantitative trait loci (QTL) was analyzed. This analysis revealed overall a more active immune response in WKY than LEW rats. Important differences were observed in the association of DEG with QTL in LEW vs. WKY rats. Both the number of upregulated DEG associated with rat arthritis-QTL and their level of expression were relatively higher in LEW when compared to WKY rat; however, the number of downregulated DEG-associated with rat arthritis-QTL as well as AIA-QTL were found to be higher in WKY than in LEW rats. In conclusion, distinct gene expression profiles define arthritis-susceptible versus resistant phenotype of MHC-compatible inbred rats. These results would advance our understanding of the pathogenesis of autoimmune arthritis and might also offer potential novel targets for therapeutic purposes.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Changwan
authors.initials: C
authors.lastname: Lu
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tan
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology; D016000:Cluster Analysis; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D013045:Species Specificity; D059467:Transcriptome / Q000276:immunology*
chemical_list: D000941:Antigens; D001426:Bacterial Proteins; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium
keywords: AIA; Antigen-induced T cell response; Antigen-induced response; Autoimmune arthritis; Bhsp65; CIA; DEG; Disease resistant; Disease susceptibility; Experimental arthritis; Gene expression profiling; Heat-shock proteins; IFN; IL; Inc; LEW; LNC; Lewis; Lymphoid cells; Med; Microarray analysis; Mtb; Mycobacterium tuberculosis H37Ra; OIA; PIA; QTL; RA; Rat adjuvant arthritis; SCWIA; WKY; Wistar Kyoto; adjuvant-induced arthritis; collagen-induced arthritis; differentially expressed gene; incubation; interferon; interleukin; lymph node cells; medium; mycobacterial heat-shock protein 65; oil-induced arthritis; pristane-induced arthritis; qPCR; quantitative real-time PCR; quantitative trait locus; rheumatoid arthritis; streptococcal cell wall-induced arthritis
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