First Author | Turchinovich G | Year | 2011 |
Journal | Immunity | Volume | 35 |
Issue | 1 | Pages | 59-68 |
PubMed ID | 21737317 | Mgi Jnum | J:174553 |
Mgi Id | MGI:5139961 | Doi | 10.1016/j.immuni.2011.04.018 |
Citation | Turchinovich G, et al. (2011) Skint-1 Identifies a Common Molecular Mechanism for the Development of Interferon-gamma-Secreting versus Interleukin-17-Secreting gammadelta T Cells. Immunity 35(1):59-68 |
abstractText | Murine T cell development begins with the generation of a unique Vgamma5(+)Vdelta1(+) epidermal gammadelta T cell compartment and a unique, more broadly distributed Vgamma6(+)Vdelta1(+) subset that is an important source of interleukin-17 (IL-17). This study showed that these respective functional programs were determined by Skint-1, a thymic epithelial cell determinant. By engaging Skint-1(+) cells, Vgamma5(+)Vdelta1(+) thymocytes induced an Egr3-mediated pathway, provoking differentiation and the potential to produce IFN-gamma while suppressing the gammadelta T cell lineage factor, Sox13, and a RORgammat transcription factor-associated IL-17-producing capacity. Hence, the functions of the earliest T cells are substantially preprogrammed in the thymus. Additionally, the phenotype of Skint-1-selected fetal thymocytes permitted identification in the adult thymus of an analogous gene regulatory network regulated by the gammadelta T cell receptor. Hence, these observations describe a molecular pathway by which distinct stress-responsive lymphocyte repertoires may emerge throughout ontogeny and offer parallels with emerging perspectives on the functional selection of other lymphoid cells. |