Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus
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 thym...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01629/full |
| _version_ | 1811270546425380864 |
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| author | Konstantinos Mengrelis Ching-In Lau Jasmine Rowell Anisha Solanki Sonia Norris Susan Ross Masahiro Ono Susan Outram Tessa Crompton |
| author_facet | Konstantinos Mengrelis Ching-In Lau Jasmine Rowell Anisha Solanki Sonia Norris Susan Ross Masahiro Ono Susan Outram Tessa Crompton |
| author_sort | Konstantinos Mengrelis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:02:42Z |
| format | Article |
| id | doaj.art-4328ac17533e4de091c065c06209e14a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T22:02:42Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4328ac17533e4de091c065c06209e14a2022-12-22T03:15:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01629449731Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the ThymusKonstantinos Mengrelis0Ching-In Lau1Jasmine Rowell2Anisha Solanki3Sonia Norris4Susan Ross5Masahiro Ono6Susan Outram7Tessa Crompton8UCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomDepartment of Life Sciences, Imperial College London, London, United KingdomDepartment of Natural Sciences, Middlesex University, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomHere 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01629/fullShhγδ T-cellthymusγδNKTSmoothenedHedgehog |
| spellingShingle | Konstantinos Mengrelis Ching-In Lau Jasmine Rowell Anisha Solanki Sonia Norris Susan Ross Masahiro Ono Susan Outram Tessa Crompton Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus Frontiers in Immunology Shh γδ T-cell thymus γδNKT Smoothened Hedgehog |
| title | Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus |
| title_full | Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus |
| title_fullStr | Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus |
| title_full_unstemmed | Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus |
| title_short | Sonic Hedgehog Is a Determinant of γδ T-Cell Differentiation in the Thymus |
| title_sort | sonic hedgehog is a determinant of γδ t cell differentiation in the thymus |
| topic | Shh γδ T-cell thymus γδNKT Smoothened Hedgehog |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01629/full |
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