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

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.
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