PLZF Controls the Development of Fetal-Derived IL-17+Vγ6+ γδ T Cells

• Published in: The Journal of immunology (1950) Vol. 195; no. 9; pp. 4273 - 4281
• Main Authors: Lu, Ying, Cao, Xin, Zhang, Xianyu, Kovalovsky, Damian
• Format: Journal Article
• Language: English
• Published: United States 01-11-2015
• Subjects: Animals; Animals, Newborn; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Lineage - genetics; Cell Lineage - immunology; Fetus - cytology; Fetus - immunology; Flow Cytometry; Gene Expression Regulation, Developmental - immunology; Interleukin-17 - immunology; Interleukin-17 - metabolism; Kruppel-Like Transcription Factors - deficiency; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - immunology; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Promyelocytic Leukemia Zinc Finger Protein; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - immunology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thymocytes - immunology; Thymocytes - metabolism; Thymus Gland - embryology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500939

Expression of promyelocytic leukemia zinc finger (PLZF) protein directs the effector differentiation of invariant NKT (iNKT) cells and IL-4(+) γδ NKT cells. In this study, we show that PLZF is also required for the development and function of IL-17(+) γδ T cells. We observed that PLZF is expressed in fetal-derived invariant Vγ5(+) and Vγ6(+) γδ T cells, which secrete IFN-γ and IL-17, respectively. PLZF deficiency specifically affected the effector differentiation of Vγ6(+) cells, leading to reduced numbers of mature CD27(-)CD44(+) phenotype capable of secreting IL-17. Although PLZF was not required for Vγ5(+) γδ T cells to develop, when these cells were reprogrammed into IL-17-secreting cells in Skint-1 mutant mice, they required PLZF for their effector maturation, similarly to Vγ6(+) γδ T cells. The impaired effector differentiation of PLZF-deficient Vγ6(+) γδ T cells was not due to increased apoptosis and it was related to reduced proliferation of immature CD27(+)CD44(-) Vγ6(+) γδ T cells, which was required for their differentiation into mature CD27(-)CD44(+) IL-17-secreting cells. Thus, the present study identifies that PLZF function is not restricted to NKT or IL-4(+) T cells, but it also controls the development of IL-17(+) γδ T cells.