| First Author | Mengrelis K | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 1629 | PubMed ID | 31379834 |
| Mgi Jnum | J:298319 | Mgi Id | MGI:6472201 |
| Doi | 10.3389/fimmu.2019.01629 | Citation | Mengrelis K, et al. (2019) Sonic Hedgehog Is a Determinant of gammadelta T-Cell Differentiation in the Thymus. Front Immunol 10:1629 |
| abstractText | Here we investigate the function of Hedgehog (Hh) signaling in thymic gammadelta T-cell maturation and subset differentiation. Analysis of Hh mutants showed that Hh signaling promotes gammadelta T-cell development in the thymus and influences gammadelta T-cell effector subset distribution. Hh-mediated transcription in thymic gammadelta cells increased gammadelta T-cell number, and promoted their maturation and increased the gammadeltaNKT subset, whereas inhibition of Hh-mediated transcription reduced the thymic gammadelta T-cell population and increased expression of many genes that are normally down-regulated during gammadelta T-cell maturation. These changes were also evident in spleen, where increased Hh signaling increased gammadeltaNKT cells, but reduced CD27-CD44+ and Vgamma2+ populations. Systemic in vivo pharmacological Smoothened-inhibition reduced gammadelta T-cell and gammadeltaNKT cells in the thymus, and also reduced splenic gammadelta T-cell and gammadeltaNKT populations, indicating that Hh signaling also influences homeostasis of peripheral gammadelta T-cell populations. Taken together our data indicate that Sonic Hedgehog is an important determinant of gammadelta T-cell effector subset differentiation. |