TY - JOUR
T1 - Transcriptomes of antigen presenting cells in human thymus
AU - Gabrielsen, Ingvild S.M.
AU - Helgeland, Hanna
AU - Akselsen, Helle
AU - Aass, Hans Christian D.
AU - Sundaram, Arvind Y.M.
AU - Snowhite, Isaac V.
AU - Pugliese, Alberto
AU - Flåm, Siri T.
AU - Lie, Benedicte A.
N1 - Funding Information:
This study was financed by the Research Council of Norway (214280/F20) (https://www. forskningsradet.no/) and the Norwegian Diabetes Association (https://www.diabetes.no/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank Harald Lindberg at Oslo University Hospital for providing the thymus tissues, the Norwegian Sequencing Center (NSC) for RNA sequencing our APC samples. This study was financed by the Research Council of Norway (214280/F20) and the Norwegian Diabetes Association.
Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Antigen presenting cells (APCs) in the thymus play an essential role in the establishment of central tolerance, i.e. the generation of a repertoire of functional and self-tolerant T cells to prevent autoimmunity. In this study, we have compared the transcriptomes of four primary APCs from human thymus (mTECs, CD19+ B cells, CD141+ and CD123+ DCs). We investigated a set of genes including the HLA genes, genes encoding transcriptional regulators and finally, tissue-enriched genes, i.e, genes with a five-fold higher expression in a particular human tissue. We show that thymic CD141+ DCs express the highest levels of all classical HLA genes and 67% (14/21) of the HLA class I and II pathway genes investigated in this study. CD141+ DCs also expressed the highest levels of the transcriptional regulator DEAF1, whereas AIRE and FEZF2 expression were mainly found in primary human mTECs. We found expression of “tissue enriched genes” from the Human Protein Atlas (HPA) in all four APC types, but the mTECs were clearly dominating in the number of uniquely expressed tissue enriched genes (20% in mTECs, 7% in CD19+ B cells, 4% in CD123+ DCs and 2% in CD141+ DCs). The tissue enriched genes also overlapped with reported human autoantigens. This is, to our knowledge, the first study that performs RNA sequencing of mTECs, CD19+ B cells, CD141+ and CD123+ DCs isolated from the same individuals and provides insight into the transcriptomes of these human thymic APCs.
AB - Antigen presenting cells (APCs) in the thymus play an essential role in the establishment of central tolerance, i.e. the generation of a repertoire of functional and self-tolerant T cells to prevent autoimmunity. In this study, we have compared the transcriptomes of four primary APCs from human thymus (mTECs, CD19+ B cells, CD141+ and CD123+ DCs). We investigated a set of genes including the HLA genes, genes encoding transcriptional regulators and finally, tissue-enriched genes, i.e, genes with a five-fold higher expression in a particular human tissue. We show that thymic CD141+ DCs express the highest levels of all classical HLA genes and 67% (14/21) of the HLA class I and II pathway genes investigated in this study. CD141+ DCs also expressed the highest levels of the transcriptional regulator DEAF1, whereas AIRE and FEZF2 expression were mainly found in primary human mTECs. We found expression of “tissue enriched genes” from the Human Protein Atlas (HPA) in all four APC types, but the mTECs were clearly dominating in the number of uniquely expressed tissue enriched genes (20% in mTECs, 7% in CD19+ B cells, 4% in CD123+ DCs and 2% in CD141+ DCs). The tissue enriched genes also overlapped with reported human autoantigens. This is, to our knowledge, the first study that performs RNA sequencing of mTECs, CD19+ B cells, CD141+ and CD123+ DCs isolated from the same individuals and provides insight into the transcriptomes of these human thymic APCs.
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U2 - 10.1371/journal.pone.0218858
DO - 10.1371/journal.pone.0218858
M3 - Article
C2 - 31261375
AN - SCOPUS:85069269240
VL - 14
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0218858
ER -