title: Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells.
abstract: Murine T cell development begins with the generation of a unique Vγ5(+)Vδ1(+) epidermal γδ T cell compartment and a unique, more broadly distributed Vγ6(+)Vδ1(+) 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, Vγ5(+)Vδ1(+) thymocytes induced an Egr3-mediated pathway, provoking differentiation and the potential to produce IFN-γ while suppressing the γδ T cell lineage factor, Sox13, and a RORγt 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 γδ 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.
authors: London Research Institute, Cancer Research UK, and Peter Gorer Department of Immunobiology, King's College School of Medicine at Guy's Hospital, London SE1 9RT, UK.
authors: Gleb
authors: G
authors: Turchinovich
authors: Adrian C
authors: AC
authors: Hayday
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D051776:Early Growth Response Protein 3 / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology*
chemical_list: D001324:Autoantigens; C497369:Egr3 protein, mouse; D007136:Immunoglobulins; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; C529023:Skint1 protein, mouse; C110455:Sox13 protein, mouse; D051776:Early Growth Response Protein 3; D007371:Interferon-gamma