Frontiers in Immunology (Jul 2019)

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

  • Konstantinos Mengrelis,
  • Ching-In Lau,
  • Jasmine Rowell,
  • Anisha Solanki,
  • Sonia Norris,
  • Susan Ross,
  • Masahiro Ono,
  • Susan Outram,
  • Tessa Crompton

DOI
https://doi.org/10.3389/fimmu.2019.01629
Journal volume & issue
Vol. 10

Abstract

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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.

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