Differential expression of transcripts for the autoimmunity-related human dendritic cell immunoreceptor.
Dendritic cell immunoreceptor (DCIR) deficiency is related to development of autoimmune disorders and DCIR gene polymorphisms are associated with rheumatoid arthritis (RA). We analyzed the mRNA expression from the four known transcripts of DCIR in IFN-gamma-treated human leukocytes together with fine mapping across the locus. RA patients and healthy controls were genotyped for several single nucleotide polymorphisms (SNPs) in DCIR and flanking regions. mRNA expression in peripheral blood mononuclear cells (PBMCs), stimulated with gamma-interferon (IFN-gamma) in vitro, was determined by transcript-specific PCR. Our data reveal that IFN-gamma significantly downregulates the average expression of transcripts DCIR_v1, DCIR_v2, DCIR_v3 and DCIR_v4 (P<0.0001 for v1, P<0.02 for v2, P<0.0001 for v3, P<0.001 for _v4, patients and controls, Wilcoxon signed-rank). The expression of DCIR showed significant association with variations in the gene. Cells with the RA-associated allele rs2024301 exhibit a significant increase in the expression of DCIR_v4. We also present a new fifth isoform lacking exons 2, 3 and 4. This data illustrate that common genetic variations may influence DCIR mRNA expression. We also show that the expression is regulated by the inflammatory mediator IFN-gamma, affecting all four transcripts and that this was independent of genotype.
Ronninger
M
M
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. marcus.ronninger@ki.se
Eklöw
C
C
Lorentzen
J C
JC
Klareskog
L
L
Padyukov
L
L
D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D037181:Lectins, C-Type / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C423004:CLEC4A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014157:Transcription Factors; D007371:Interferon-gamma