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Transcriptomes of antigen presenting cells in human thymus
Author(s) -
Ingvild Gabrielsen,
Hanna Helgeland,
Helle Akselsen,
Hans Christian Dalsbotten Aass,
Arvind Sundaram,
Isaac Snowhite,
Alberto Pugliese,
Siri Tennebø Flåm,
Benedicte A. Lie
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0218858
Subject(s) - transcriptome , biology , gene , human leukocyte antigen , cd19 , antigen , microbiology and biotechnology , genetics , gene expression
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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