Oncotarget

Research Papers: Immunology:

Comparative analysis of human and mouse transcriptomes of Th17 cell priming

Soile Tuomela, Sini Rautio, Helena Ahlfors, Viveka Öling, Verna Salo, Ubaid Ullah, Zhi Chen, Saara Hämälistö, Subhash K. Tripathi, Tarmo Äijö, Omid Rasool, Hayssam Soueidan, Lodewyk Wessels, Brigitta Stockinger, Harri Lähdesmäki, Riitta Lahesmaa _

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Oncotarget. 2016; 7:13416-13428. https://doi.org/10.18632/oncotarget.7963

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Abstract

Soile Tuomela1,*, Sini Rautio2,*, Helena Ahlfors3,*, Viveka Öling1,*, Verna Salo1, Ubaid Ullah1, Zhi Chen1, Saara Hämälistö1, Subhash K. Tripathi1, Tarmo Äijö2, Omid Rasool1, Hayssam Soueidan4, Lodewyk Wessels4, Brigitta Stockinger3,**, Harri Lähdesmäki1,2,** and Riitta Lahesmaa1,**

1 Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

2 Department of Computer Science, Aalto University, Espoo, Finland

3 Division of Molecular Immunology, MRC National Institute for Medical Research, London, United Kingdom

4 Computational Cancer Biology, Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands

* These authors have contributed equally to this work and as first authors

** These authors have contributed equally to this work and as last authors

Correspondence to:

Riitta Lahesmaa, email:

Keywords: Th17 cell priming, RNA-seq, comparative analysis of human and mouse, lncRNA, disease-associated SNPs, Immunology and Microbiology Section, Immune response, Immunity

Received: September 18, 2015 Accepted: February 24, 2016 Published: March 07, 2016

Abstract

Uncontrolled Th17 cell activity is associated with cancer and autoimmune and inflammatory diseases. To validate the potential relevance of mouse models of targeting the Th17 pathway in human diseases we used RNA sequencing to compare the expression of coding and non-coding transcripts during the priming of Th17 cell differentiation in both human and mouse. In addition to already known targets, several transcripts not previously linked to Th17 cell polarization were found in both species. Moreover, a considerable number of human-specific long non-coding RNAs were identified that responded to cytokines stimulating Th17 cell differentiation. We integrated our transcriptomics data with known disease-associated polymorphisms and show that conserved regulation pinpoints genes that are relevant to Th17 cell-mediated human diseases and that can be modelled in mouse. Substantial differences observed in non-coding transcriptomes between the two species as well as increased overlap between Th17 cell-specific gene expression and disease-associated polymorphisms underline the need of parallel analysis of human and mouse models. Comprehensive analysis of genes regulated during Th17 cell priming and their classification to conserved and non-conserved between human and mouse facilitates translational research, pointing out which candidate targets identified in human are worth studying by using in vivo mouse models.


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