Sonic Hedgehog is a determinant of γδ T-Cell differentiation in the Thymus

Mengrelis, Konstantinos, Lau, Ching-In, Rowell, Jasmine, Solanki, Anisha, Norris, Sonia, Ross, Susan, Ono, Masahiro, Outram, Susan and Crompton, Tessa (2019) Sonic Hedgehog is a determinant of γδ T-Cell differentiation in the Thymus. Frontiers in Immunology, 10 , 1629. pp. 1-17. ISSN 1664-3224 [Article] (doi:10.3389/fimmu.2019.01629)

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Abstract

Here we investigate the function of Hedgehog (Hh) signaling in thymic γδ T-cell maturation and subset differentiation. Analysis of Hh mutants showed that Hh signaling promotes γδ T-cell development in the thymus and influences γδ T-cell effector subset distribution. Hh-mediated transcription in thymic γδ cells increased γδ T-cell number, and promoted their maturation and increased the γδNKT subset, whereas inhibition of Hh-mediated transcription reduced the thymic γδ T-cell population and increased expression of many genes that are normally down-regulated during γδ T-cell maturation. These changes were also evident in spleen, where increased Hh signaling increased γδNKT cells, but reduced CD27-CD44+ and Vγ2+ populations. Systemic in vivo pharmacological Smoothened-inhibition reduced γδ T-cell and γδNKT cells in the thymus, and also reduced splenic γδ T-cell and γδNKT populations, indicating that Hh signaling also influences homeostasis of peripheral γδ T-cell populations. Taken together our data indicate that Sonic Hedgehog is an important determinant of γδ T-cell effector subset differentiation.

Item Type: Article
Keywords (uncontrolled): Immunology, Shh, γδ T-cell, thymus, γδNKT, Smoothened, Hedgehog
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 27274
Notes on copyright: Copyright © 2019 Mengrelis, Lau, Rowell, Solanki, Norris, Ross, Ono, Outram and Crompton. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
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Depositing User: Jisc Publications Router
Date Deposited: 02 Aug 2019 15:14
Last Modified: 20 Aug 2020 22:50
URI: https://eprints.mdx.ac.uk/id/eprint/27274

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