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

Abstract

SummaryThe thymus is responsible for generating a diverse yet self-tolerant T cell pool 1. While the thymic medulla is largely composed of developing and mature AIRE+ epithelial cells, recent evidence suggests far greater heterogeneity amongst medullary thymic epithelial cells than previously appreciated 2. Here we describe in detail an epithelial subset which shares striking similarity to peripheral tuft cells found at mucosal barriers 3. As in the periphery, thymic tuft cells express the canonical taste transduction pathway and IL25. However, they are unique in their spatial association with cornified aggregates, ability to present antigen, 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. Remarkably, the taste chemosensory protein TRPM5 is required for their thymic function where they support the development and polarization of thymic iNKT cells and act to establish a medullary microenvironment enriched in the type 2 cytokine, IL4. These findings suggest a compartmentalized medullary environment where differentiation of a minor and highly-specialized epithelial subset plays a non-redundant role in shaping thymic function.