Journal Article

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

Wigton, Eric J., Miller, Corey N., Rattay, Kristin, Fries, Adam C., Proekt, Irina, Parent, Audrey V., Anderson, Mark S., Kyewski, Bruno, Pollack, Joshua L., Metzger, Todd C., Steinmetz, Lars M., Wells, Kristen L., Hogquist, Kristin A., Lwin, Wint W., Wang, Haiguang, von Moltke, Jakob, Rajpurkar, Aparna R., Khan, Imran S., Erle, David J., Locksley, Richard M.

2018

Overview

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells 1 . 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 thought 2 . Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers 3 . 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. A comprehensive analysis of the thymic medulla identifies a tuft-cell-like thymic epithelial cell population that is necessary for shaping thymic function.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/31 / 13/51 / 14/19 / 38/35 / 38/91 / 631/250/1619/554/383 / 631/250/1620/1840 / 631/250/2152/1566/2493 / 631/250/2503 / 64/60 / 96/1 / 96/34 / AIRE Protein / Animals / Antigens / Bioinformatics / Cell development (Biology) / Cellular Microenvironment / Chemoreception / Cytokines / Doublecortin-Like Kinases / Epithelial cells / Epithelial Cells - cytology / Epithelial Cells - metabolism / Female / Gene expression / Heterogeneity / HIPK2 protein / Humanities and Social Sciences / Humans / Immune Tolerance - immunology / Interleukin 4 / Interleukin-4 - biosynthesis / Interleukin-4 - metabolism / Interleukins - metabolism / Intracellular Signaling Peptides and Proteins - metabolism / Kinases / Letter / Lymphocytes / Lymphocytes T / Male / Medulla oblongata / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Morphology / Mucosa / multidisciplinary / Natural killer cells / Observations / Physiological aspects / Protein Serine-Threonine Kinases - metabolism / Proteins / Receptors / Science / Science (multidisciplinary) / Signal transduction / T cells / Taste / Taste receptors / Taste transduction / Thymocytes - cytology / Thymocytes - metabolism / Thymus / Thymus Gland - anatomy & histology / Thymus Gland - cytology / Thymus Gland - metabolism / Transcription Factors - deficiency / Transcription Factors - genetics / Transient receptor potential proteins / TRPM Cation Channels - metabolism