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000136766 1001_ $$aMiller, Corey N$$b0
000136766 245__ $$aThymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.
000136766 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2018
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000136766 520__ $$aThe thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.
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000136766 7001_ $$aProekt, Irina$$b1
000136766 7001_ $$avon Moltke, Jakob$$b2
000136766 7001_ $$aWells, Kristen L$$b3
000136766 7001_ $$aRajpurkar, Aparna R$$b4
000136766 7001_ $$aWang, Haiguang$$b5
000136766 7001_ $$0P:(DE-He78)83227bd2ef5cb3bccf76dc974c9ad2cc$$aRattay, Kristin$$b6$$udkfz
000136766 7001_ $$aKhan, Imran S$$b7
000136766 7001_ $$aMetzger, Todd C$$b8
000136766 7001_ $$aPollack, Joshua L$$b9
000136766 7001_ $$aFries, Adam C$$b10
000136766 7001_ $$aLwin, Wint W$$b11
000136766 7001_ $$aWigton, Eric J$$b12
000136766 7001_ $$aParent, Audrey V$$b13
000136766 7001_ $$0P:(DE-He78)08a57258198dcedd8ff8ac7eef40341a$$aKyewski, Bruno$$b14$$udkfz
000136766 7001_ $$aErle, David J$$b15
000136766 7001_ $$aHogquist, Kristin A$$b16
000136766 7001_ $$aSteinmetz, Lars M$$b17
000136766 7001_ $$aLocksley, Richard M$$b18
000136766 7001_ $$aAnderson, Mark S$$b19
000136766 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-018-0345-2$$gVol. 559, no. 7715, p. 627 - 631$$n7715$$p627 - 631$$tNature <London>$$v559$$x1476-4687$$y2018
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