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Differential transcriptome of tolerogenic versus inflammatory dendritic cells points to modulated T1D genetic risk and enriched immune regulation

Genes & Immunity volume 18, pages 176–183 (2017)Cite this article

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Abstract

Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD3/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators. Gene expression differences correlated with protein expression, designating low CD86 and high CD52 on the cell surface as superior discriminators between tolDCs and mDCs. Of 37 candidate genes conferring risk to developing type 1 diabetes (T1D), 11 genes differentially expressed in tolDCs and mDCs regulated immune response and antigen-presenting activity. Differential-expressed transcripts of candidate risk loci for T1D suggest a role of these ‘risk genes’ in immune regulation, which targeting may modulate the genetic contribution to autoimmunity.

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Acknowledgements

This work was supported by European Union 7th Framework Programme (FP7/2007–2013) Grant 241447 (NAIMIT) and the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement 115797 (INNODIA) (this Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation program and ‘EFPIA,’ ‘JDRF,’ and ‘The Leona M. and Harry B. Helmsley Charitable Trust.’), Netherlands Organization for Scientific Research Vici Grant 918.86.611, the Dutch Arthritis Foundation (LLP16) and by an Expert Center Grant from the Dutch Diabetes Research Foundation.

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Author notes

  1. T Nikolic and N J C Woittiez: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    T Nikolic, N J C Woittiez, A van der Slik, S Laban, A Joosten, J J Zwaginga & B O Roep

  2. Department of Clinical and Experimental Endocrinology, University of Leuven, Leuven, Belgium

    C Gysemans & C Mathieu

  3. Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    B Koeleman

  4. Department of Diabetes Immunology, Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA, USA

    B O Roep

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  1. T Nikolic
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  2. N J C Woittiez
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Correspondence to T Nikolic.

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Nikolic, T., Woittiez, N., van der Slik, A. et al. Differential transcriptome of tolerogenic versus inflammatory dendritic cells points to modulated T1D genetic risk and enriched immune regulation. Genes Immun 18, 176–183 (2017). https://doi.org/10.1038/gene.2017.18

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