Journal
NATURE
Volume 559, Issue 7715, Pages 627-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-018-0345-2
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Funding
- NIH [R01 AI097457, R37 AI039560, U01 DK107383, P01 HG00020527, R01 AI026918, 1S10OD021822-01]
- Larry Hillblom Foundation [2017-D-012-FEL]
- NIH Medical Scientist Training Program [T32 GM007618]
- NSF [GRFP DGE 1656518]
- Damon Runyon Cancer Research Foundation [DRG-2162-13]
- Howard Hughes Medical Institute
- Sandler Asthma Basic Research Center
- German Cancer Research Center
- European Research Council [ERC-2012-AdG]
- NIH Diabetes Research Center [P30 DK063720]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL107202] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007334, R37AI097457, R01AI026918, R01AI097457, R37AI039560] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK107383, P30DK063720] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007618, T32GM007790] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD021822] Funding Source: NIH RePORTER
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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.
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