Review Article | Published:

Generation of diversity in thymic epithelial cells

Nature Reviews Immunology volume 17, pages 295305 (2017) | Download Citation

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Abstract

In the thymus, diverse populations of thymic epithelial cells (TECs), including cortical and medullary TECs and their subpopulations, have distinct roles in coordinating the development and repertoire selection of functionally competent and self-tolerant T cells. Here, we review the expanding diversity in TEC subpopulations in relation to their functions in T cell development and selection as well as their origins and development.

Key points

  • Cortical thymic epithelial cells (cTECs) are functionally heterogeneous, although T cell-lineage-specifying and positive-selection-inducing functions seem to overlap between individual cTECs.

  • Thymic nurse cells are a subpopulation of cTECs that are morphologically and functionally specialized for optimizing the positive selection of thymocytes.

  • Promiscuous gene expression in individual medullary TECs (mTECs) is heterogeneous, and mosaic expression across all mTECs constitutes a pool of the promiscuously expressed genes.

  • CC-chemokine ligand 21 (CCL21)-expressing mTECs represent a functionally mature mTEClow subpopulation and resemble post-autoimmune regulator (AIRE) mTECs.

  • Embryonic TEC progenitors acquire hallmarks of the cTEC lineage and then the mTEC lineage in a stepwise manner during initial thymus cortex and medulla formation.

  • A self-renewing subset of embryonic TECs, referred to as mTEC stem cells, has been identified that are capable of long-term and specific generation of mTECs.

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Acknowledgements

The Takahama laboratory is supported by grants from the Ministry of Education, Culture, Sports, Science and Technology–Japan Society for the Promotion of Science (MEXT–JSPS; 24111004 and 16H02630 to Y.T. and 15K19130 to I.O.). The Anderson laboratory is supported by a UK Medical Research Council (MRC) Programme grant and a Cancer Research UK (CRUK) Cancer Immunology grant. The Takahama and Anderson laboratories have received joint support from The Royal Society, The Daiwa Anglo-Japanese Foundation and the MEXT–JSPS (the MEXT Joint Usage Research Center Program and the JSPS Open Partnership Joint Project).

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Affiliations

  1. Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima 770-8503, Japan.

    • Yousuke Takahama
    •  & Izumi Ohigashi
  2. Institute for Immunology and Immunotherapy, Medical School, University of Birmingham, Birmingham B15 2TT, UK.

    • Song Baik
    •  & Graham Anderson

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yousuke Takahama.

Glossary

Positive selection

The process by which newly generated double-positive thymocytes that interact at low affinity with self-peptide—MHC complexes presented by cortical thymic epithelial cells are induced to survive and differentiate into single-positive thymocytes.

Hassall's corpuscles

A fraction of medullary thymic epithelial cells that form a concentric epithelial structure, which is apparent in the thymus of several limited species, including humans.

Autoimmune regulator

(AIRE). A nuclear protein that is expressed by a subpopulation of medullary thymic epithelial cells and is essential for the establishment of self-tolerance in T cells.

Promiscuous gene expression

A characteristic unique to medullary thymic epithelial cells, in which virtually all genes, including tissue-restricted self-antigens, are expressed.

nude mouse

A naturally occurring mouse strain in which congenital loss of the transcription factor Forkhead box N1 causes defective hair growth and defective thymic epithelial cell development, resulting in defective T cell production and severe immunodeficiency.

Thymic atrophy

A reduction in the size of the thymus that can be caused by ageing, viral infection, irradiation and many other stresses and is associated with a decline in T cell production.

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https://doi.org/10.1038/nri.2017.12

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