KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/660340
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AbstractGM-CSF produced by autoreactive CD4 positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as Multiple Sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF producing CD4 T cells from human peripheral blood by using a cytokine capture assay. We compared these cells to the corresponding GM-CSF negative fraction, and furthermore, we studied naïve CD4 T cells, memory CD4 T cells and bulk CD4 T cells from the same individuals as additional control cell populations. As a result, we provide a rich resource of integrated chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) data from these primary human CD4 T cell subsets, and we show that the identified signatures are associated with human autoimmune disease, especially Multiple Sclerosis. By combining information about mRNA expression, DNA accessibility and predicted transcription factor binding, we reconstructed directed gene regulatory networks connecting transcription factors to their targets, which comprise putative key regulators of human GM-CSF positive CD4 T cells as well as memory CD4 T cells. Our results suggest potential therapeutic targets to be investigated in the future in human autoimmune disease.
CitationElias, S., Schmidt, A., Gomez-Cabrero, D., & Tegner, J. (2019). Gene regulatory network of human GM-CSF secreting T helper cells. doi:10.1101/555433
SponsorsThe authors thank Matilda Eriksson and Peri Noori for performing RNA extractions, library preparation and quality control for RNA-seq, and next-generation sequencing, as well as for excellent general lab management; Sunjay Jude Fernandes for reagents and advice for the ATAC-seq protocol; and Gilad Silberberg for helpful discussions about footprinting and motif scanning (all from Computational Medicine Unit, Karolinska Institute). We thank John Andersson (Translational Immunology Unit, Karolinska Institute) for helpful suggestions and discussions.
This work was supported by Karolinska Institute’s faculty funds for doctoral education [KID-funding to S.E.]; the Center of Excellence for Research on Inflammation and Cardiovascular disease [CERIC, to A.S. and J.T.]; the 7th European Community Framework Programme [FP7-PEOPLE project 326930 to A.S.; FP7-IDEAS-ERC project 617393 to S.E., A.S., J.T. and D.G.C.; FP7-HEALTH project 306000 to J.T. and D.G.C.]; Vetenskapsrådet Medicine and Health [2011-3264 to J.T.]; and Torsten Söderberg Foundation [to J.T.].
PublisherCold Spring Harbor Laboratory