Regulation of Gene Expression in Autoimmune Disease Loci and the Genetic Basis of Proliferation in CD4 Effector Memory T Cells

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Genome-wide association studies have identified hundreds of genetic variants associated to autoimmune diseases. To understand the mechanisms and pathways affected by these variants, follow-up studies of molecular phenotypes and functions are required. Given the diversity of cell types and specialization of functions within the immune system, it is crucial that such studies focus on specific and relevant cell types. Here, we studied genetic and cellular traits of CD4-positive effector memory T (CD4+ TEM) cells, which are particularly important in the onset of rheumatoid arthritis, celiac disease, and type 1 diabetes. In a cohort of healthy individuals, we purified CD4+ TEM cells, assayed genome-wide single nucleotide polymorphisms (SNPs), abundance of CD4+ TEM cells in blood, proliferation upon T cell receptor stimulation, and 215 gene transcripts in resting and stimulated states. We found that expression levels of 46 genes were regulated by nearby SNPs, including disease-associated SNPs. Many of these expression quantitative trait loci were not previously seen in studies of more heterogeneous peripheral blood cells. We demonstrated that relative abundance and proliferative response of CD4+ TEM cells varied in the population, however disease alleles are unlikely to confer risk by modulating these traits in this cell type.

Vyšlo v časopise: Regulation of Gene Expression in Autoimmune Disease Loci and the Genetic Basis of Proliferation in CD4 Effector Memory T Cells. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004404
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004404

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