Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigen presentation by the MHC-II to CD4+ T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2q ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function. We demonstrate that an allelic variant in the type I promoter of C2ta resulted in an increased expression of MHC-II on macrophages (72-151% higher mean florescence intensity) and conventional dendritic cells (13-65% higher mean florescence intensity) in both spleen and peripheral blood. The increase in MHC-II expression resulted in an increase in antigen presentation to T cells in vitro and increased T-cell activation. The differential MHC-II expression in B6Q.C2ta, however, did not alter the disease development in models of rheumatoid arthritis (collagen-induced arthritis and human glucose-6-phosphate-isomerase325-339 -peptide-induced arthritis), or multiple sclerosis (MOG1-125 protein-induced and MOG79-96 peptide-induced experimental autoimmune encephalomyelitis). This is the first study to address the role of an allelic variant in type I promoter of C2ta in MHC-II expression and autoimmune diseases; and shows that C2ta polymorphisms regulate MHC-II expression and T-cell responses but do not necessarily have a strong impact on autoimmune diseases.
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PMID:Effects of C2ta genetic polymorphisms on MHC class II expression and autoimmune diseases. 2786 21