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

Corey N. Miller, Irina Proekt, Jakob Moltke, Kristen L. Wells, Aparna R. Rajpurkar, Haiguang Wang, Kristin Rattay, Imran S. Khan, Todd C. Metzger, Joshua L. Pollack, Adam C. Fries, Wint W. Lwin, Eric J. Wigton, Audrey V. Parent, Bruno Kyewski, David J. Erle, Kristin A. Hogquist, Lars M. Steinmetz, Richard M. Locksley and Mark S. Anderson ()
Additional contact information
Corey N. Miller: Diabetes Center, University of California, San Francisco
Irina Proekt: Diabetes Center, University of California, San Francisco
Jakob Moltke: University of California, San Francisco
Kristen L. Wells: Stanford University School of Medicine
Aparna R. Rajpurkar: Stanford University School of Medicine
Haiguang Wang: University of Minnesota
Kristin Rattay: Tumor Immunology Program, German Cancer Research Center (DKFZ)
Imran S. Khan: Diabetes Center, University of California, San Francisco
Todd C. Metzger: Diabetes Center, University of California, San Francisco
Joshua L. Pollack: University of California, San Francisco
Adam C. Fries: University of California
Wint W. Lwin: Diabetes Center, University of California, San Francisco
Eric J. Wigton: University of California, San Francisco
Audrey V. Parent: Diabetes Center, University of California, San Francisco
Bruno Kyewski: Tumor Immunology Program, German Cancer Research Center (DKFZ)
David J. Erle: University of California, San Francisco
Kristin A. Hogquist: University of Minnesota
Lars M. Steinmetz: Stanford University School of Medicine
Richard M. Locksley: University of California, San Francisco
Mark S. Anderson: Diabetes Center, University of California, San Francisco

Nature, 2018, vol. 559, issue 7715, 627-631

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0345-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:559:y:2018:i:7715:d:10.1038_s41586-018-0345-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0345-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().