Transcriptomes of antigen presenting cells in human thymus

PLoS One. 2019 Jul 1;14(7):e0218858. doi: 10.1371/journal.pone.0218858. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / genetics
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Gene Expression Profiling
  • HLA Antigens / classification
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Humans
  • Immunophenotyping
  • Infant
  • Infant, Newborn
  • Interleukin-3 Receptor alpha Subunit / genetics
  • Interleukin-3 Receptor alpha Subunit / immunology
  • Male
  • Primary Cell Culture
  • Thrombomodulin
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcriptome / immunology*

Substances

  • APECED protein
  • Antigens, Surface
  • DEAF1 protein, human
  • DNA-Binding Proteins
  • FEZF2 protein, human
  • HLA Antigens
  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • THBD protein, human
  • Thrombomodulin
  • Transcription Factors

Grant support

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.