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Transcriptomes of antigen presenting cells in human thymus.

Ingvild S M Gabrielsen1,2, Hanna Helgeland1,2, Helle Akselsen1

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|July 2, 2019
PubMed
Summary

This study reveals distinct gene expression profiles in human thymic antigen-presenting cells (APCs). Thymic CD141+ dendritic cells (DCs) show high HLA gene expression, while mTECs uniquely express many tissue-enriched genes, crucial for preventing autoimmunity.

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Area of Science:

  • Immunology
  • Cell Biology
  • Genomics

Background:

  • Antigen-presenting cells (APCs) in the thymus are vital for establishing central tolerance, preventing autoimmunity by generating self-tolerant T cells.
  • Understanding the transcriptomic landscape of thymic APCs is crucial for elucidating mechanisms of T cell education.

Purpose of the Study:

  • To compare the transcriptomes of four primary human thymic APCs: mTECs, CD19+ B cells, CD141+ DCs, and CD123+ DCs.
  • To investigate the expression patterns of HLA genes, transcriptional regulators, and tissue-enriched genes within these APC populations.

Main Methods:

  • RNA sequencing was performed on isolated mTECs, CD19+ B cells, CD141+ DCs, and CD123+ DCs from human thymus.
  • Analysis focused on HLA genes, transcriptional regulators (e.g., DEAF1, AIRE, FEZF2), and tissue-enriched genes from the Human Protein Atlas.

Main Results:

  • Thymic CD141+ DCs exhibited the highest expression of classical HLA genes and HLA pathway genes.
  • mTECs showed predominant expression of AIRE and FEZF2, and uniquely expressed the highest proportion of tissue-enriched genes (20%).
  • Tissue-enriched genes in mTECs overlapped with known human autoantigens.

Conclusions:

  • Distinct transcriptomic profiles exist among human thymic APCs, influencing their roles in central tolerance.
  • CD141+ DCs are significant for antigen presentation via HLA molecules, while mTECs contribute uniquely to self-antigen presentation through tissue-enriched genes.