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

Author

Listed:
  • Corey N. Miller

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco)

  • Irina Proekt

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco)

  • Jakob Moltke

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    University of Washington)

  • 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)
    Harvard Medical School)

  • Imran S. Khan

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Todd C. Metzger

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco
    Bristol-Myers Squibb)

  • Joshua L. Pollack

    (University of California, San Francisco
    Pionyr Immunotherapeutics)

  • Adam C. Fries

    (University of California)

  • Wint W. Lwin

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco)

  • Eric J. Wigton

    (University of California, San Francisco)

  • Audrey V. Parent

    (Diabetes Center, University of California, San Francisco
    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
    University of California, San Francisco
    University of California, San Francisco)

  • Mark S. Anderson

    (Diabetes Center, University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

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.

Suggested Citation

  • 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. , 2018. "Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development," Nature, Nature, vol. 559(7715), pages 627-631, July.
  • Handle: RePEc:nat:nature:v:559:y:2018:i:7715:d:10.1038_s41586-018-0345-2
    DOI: 10.1038/s41586-018-0345-2
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    Citations

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    Cited by:

    1. Zhongwei Xin & Mingjie Lin & Zhixing Hao & Di Chen & Yongyuan Chen & Xiaoke Chen & Xia Xu & Jinfan Li & Dang Wu & Ying Chai & Pin Wu, 2022. "The immune landscape of human thymic epithelial tumors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Qiang Yu & Igor Gamayun & Philipp Wartenberg & Qian Zhang & Sen Qiao & Soumya Kusumakshi & Sarah Candlish & Viktoria Götz & Shuping Wen & Debajyoti Das & Amanda Wyatt & Vanessa Wahl & Fabien Ectors & , 2023. "Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Ryan N. O’Keefe & Annalisa L. E. Carli & David Baloyan & David Chisanga & Wei Shi & Shoukat Afshar-Sterle & Moritz F. Eissmann & Ashleigh R. Poh & Bhupinder Pal & Cyril Seillet & Richard M. Locksley &, 2023. "A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Fabian Klein & Clara Veiga-Villauriz & Anastasiya Börsch & Stefano Maio & Sam Palmer & Fatima Dhalla & Adam E. Handel & Saulius Zuklys & Irene Calvo-Asensio & Lucas Musette & Mary E. Deadman & Andrea , 2023. "Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Beth Lucas & Andrea J. White & Fabian Klein & Clara Veiga-Villauriz & Adam Handel & Andrea Bacon & Emilie J. Cosway & Kieran D. James & Sonia M. Parnell & Izumi Ohigashi & Yousuke Takahama & William E, 2023. "Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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