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Nature. 2018 Jul;559(7715):627-631. doi: 10.1038/s41586-018-0345-2. Epub 2018 Jul 18.

Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.

Author information

1
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
3
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
4
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
5
Department of Immunology, University of Washington, Seattle, WA, USA.
6
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
7
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
8
Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Division of Immunology, Harvard Medical School, Boston, MA, USA.
10
Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
11
Bristol-Myers Squibb, Sunnyvale, CA, USA.
12
Pionyr Immunotherapeutics, San Francisco, CA, USA.
13
Biological Imaging Development Center and Department of Pathology, University of California, San Francisco, CA, USA.
14
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA. mark.anderson@ucsf.edu.
15
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. mark.anderson@ucsf.edu.
16
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. mark.anderson@ucsf.edu.

Abstract

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.

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PMID:
30022164
PMCID:
PMC6062473
DOI:
10.1038/s41586-018-0345-2
[Indexed for MEDLINE]
Free PMC Article

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