A role for Ly108 in the induction of PLZF in developing thymocytes

• Published in: The Journal of immunology (1950) 2013-01, Vol.190 (5), p.2121-2128
• Main Authors: Dutta, Mala, Kraus, Zachary J., Gomez-Rodriguez, Julio, Hwang, Sun-hee, Cannons, Jennifer L., Cheng, Jun, Lee, Sang-Yun, Wiest, David L., Wakeland, Edward K., Schwartzberg, Pamela L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1202145

The promyelocytic zinc finger transcription factor (PLZF) is required for the development of activated phenotypes in NKT and other innate T lymphocytes. Although strong TCR stimulation has been implicated in the induction of PLZF, the factors regulating PLZF expression are incompletely understood. We show here that costimulation of pre-selection double positive thymocytes through the Signaling lymphocyte activation molecule (SLAM) family receptor Ly108 markedly enhanced PLZF expression compared to that induced by T cell receptor (TCR) stimulation alone. Costimulation with Ly108 increased expression of Egr-2 and binding of Egr-2 to the promoter of Zbtb16 , which encodes PLZF, and resulted in PLZF levels similar to those seen in NKT cells. In contrast, costimulation with αCD28 failed to enhance Egr-2 binding and Zbtb16 expression. Moreover, mice lacking Ly108 showed decreased numbers of PLZF expressing CD4 + T cells. Together, these results support a potential role for Ly108 in the induction of PLZF.