Gene expression profiling in type 1 diabetes prone NOD mice immunized with a disease protective autoantigenic peptide.
Immunization with autoantigenic peptides skews T cell responses in type 1 diabetes (T1D), yet the gene-expression signature characterizing this change is unclear. We used cDNA microarray technology to identify genes differentially regulated in splenocytes of T1D prone NOD mice after immunization with a disease protective glutamic acid decarboxylase 65 (GAD(65) P14) peptide. We identified 96 genes involved in cytokine secretion, humoral immune response, T cell activation, signal transduction, cell proliferation, complement activation and inflammatory responses. Up-regulation of seven chemokine and cytokine genes confirmed our previous findings of increased interferon-gamma (IFN-gamma) secretion, which may lead to a protective response in T1D. Hierarchical clustering was used to organize treated and control groups on the basis of their overall similarity in gene-expression patterns, suggesting association or co-regulation. Semi-quantitative RT-PCR was used to confirm the expression of selected genes in spleen and pancreatic draining lymph nodes. These findings can be used to compare other immunization strategies affecting the expression of these genes and explore their mechanisms of action. This microarray-based study, thus, unravels the molecular mechanism of beta-cell associated autoantigenic peptide immunization in T1D prone NOD mice, paving the way for identification of diagnostic markers and drug targets for modulating immune responses in T1D.
Rajput
Ashish
A
Department of Microbiology and Immunology, University of Western Ontario and Robarts Research Institute, London, Ontario N6A 5C1, Canada.
Singh
Bhagirath
B
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000627:therapeutic use; D016233:Immunotherapy, Active; D051379:Mice; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D013154:Spleen / Q000378:metabolism
D001324:Autoantigens; D010446:Peptide Fragments; C501056:glutamate decarboxylase 65 (202-221); D005968:Glutamate Decarboxylase