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Cited by 21T-cell and B-cell ImmunologyImmunotherapy and Immune Responsesvaccines and immunoinformatics approaches

Transcriptomes of antigen presenting cells in human thymus

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Gabrielsen, Ingvild S. M., Helgeland, Hanna, Akselsen, Helle, D. Aass, Hans Christian, Sundaram, Arvind Y. M., Snowhite, Isaac V., Pugliese, Alberto, Flåm, Siri T. +1 more·2019·PLOS ONE
DOI 10.1371/journal.pone.0218858PMC PMC6602790
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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.

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  • The gene for α-MyHC is not expressed in medullary thymic epithelial cells, which are crucial for negative selection during T-cell development.

    “the gene for α -MyHC is not expressed in medullary thymic epithelial cells, which are crucial for negative selection during T-cell development.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [266]

    The Introduction (page unavailable) describes mTECs as thymic antigen-presenting cells that express tissue-restricted antigens and links this process to central tolerance, supporting their role in T-cell selection. Neither that passage nor the searched passages on tissue-enriched genes state that α-MyHC (MYH6) is absent from mTECs; searches for both names found no such result. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • Autoreactive T cells that recognize α-MyHC naturally develop in every individual.

    “autoreactive T cells that recognize α -MyHC naturally develop in every individual”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [266]

    The Results section on tissue-enriched genes reports that thymic antigen-presenting cells express genes overlapping with known human autoantigen genes. Neither that passage nor the additional searches for α-MyHC, cardiac myosin, and autoreactive T-cell development address whether α-MyHC-reactive T cells naturally develop in every individual. (LLM, conf=0.74)

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Cited by

Sorted by citations

Authors
Gabrielsen, I. S. M., Helgeland, H., Akselsen, H., D. Aass, H. C., Sundaram, A. Y. M., Snowhite, I. V., Pugliese, A., Flåm, S. T., & Lie, B. A.
Affiliations
  • Oslo University Hospital (NO)
  • University of Miami (US)
Corresponding author
Gabrielsen, Ingvild S. M.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2019-07-01
Volume
14
Issue
7
Pages
e0218858
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0218858
PMC
PMC6602790
OpenAlex
W2954567461
Cited by
21
References
2
Citations by year
2026: 2 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 3
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, public-domain)
Funders
Norges Forskningsråd (214280/F20)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
antigen-presenting cells, thymus, transcriptome, medullary thymic epithelial cells, CD141+ dendritic cells, CD19+ B cells, HLA genes, central tolerance, autoimmunity, autoantigens, DEAF1, AIRE, Fezf2, Human Protein Atlas
MeSH terms
AIRE Protein, Antigens, Surface, B-Lymphocytes, Dendritic Cells, DNA-Binding Proteins, Epithelial Cells, HLA Antigens, Humans, Infant, Infant, Newborn, Male, Thymus Gland, Transcription Factors, Immunophenotyping, Antigen Presentation, Thrombomodulin, Gene Expression Profiling, Interleukin-3 Receptor alpha Subunit, Transcriptome, Primary Cell Culture

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