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Sonic Hedgehog Is a Determinant of gamma delta T-Cell Differentiation in the Thymus

Mengrelis, K; Lau, C-I; Rowell, J; Solanki, A; Norris, S; Ross, S; Ono, M; ... Crompton, T; + view all (2019) Sonic Hedgehog Is a Determinant of gamma delta T-Cell Differentiation in the Thymus. Frontiers In Immunology , 10 , Article 1629. 10.3389/fimmu.2019.01629. Green open access

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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.

Type: Article
Title: Sonic Hedgehog Is a Determinant of gamma delta T-Cell Differentiation in the Thymus
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2019.01629
Publisher version: https://doi.org/10.4000/tc.495610.3389/fimmu.2019....
Language: English
Additional information: 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 https://creativecommons.org/licenses/by/4.0/
Keywords: Shh, γδ T-cell, thymus, γδNKT, Smoothened, Hedgehog
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080726
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