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PLoS Genet. 2017 Mar 1;13(3):e1006643. doi: 10.1371/journal.pgen.1006643. eCollection 2017 Mar.

Pathogenic implications for autoimmune mechanisms derived by comparative eQTL analysis of CD4+ versus CD8+ T cells.

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Estonian Genome Center, University of Tartu, Tartu, Estonia.
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
Partners Center for Personalized Genetic Medicine, Boston, MA, United States of America.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States of America.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.


Inappropriate activation or inadequate regulation of CD4+ and CD8+ T cells may contribute to the initiation and progression of multiple autoimmune and inflammatory diseases. Studies on disease-associated genetic polymorphisms have highlighted the importance of biological context for many regulatory variants, which is particularly relevant in understanding the genetic regulation of the immune system and its cellular phenotypes. Here we show cell type-specific regulation of transcript levels of genes associated with several autoimmune diseases in CD4+ and CD8+ T cells including a trans-acting regulatory locus at chr12q13.2 containing the rs1131017 SNP in the RPS26 gene. Most remarkably, we identify a common missense variant in IL27, associated with type 1 diabetes that results in decreased functional activity of the protein and reduced expression levels of downstream IRF1 and STAT1 in CD4+ T cells only. Altogether, our results indicate that eQTL mapping in purified T cells provides novel functional insights into polymorphisms and pathways associated with autoimmune diseases.

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