The Journal of Immunology, 2007, 178: B102.
Copyright © 2007 by The American Association of Immunologists, Inc.
IRF4 Expression Defines Th2 Populations Secreting High Levels of IL-10
Ayele-Nati Nathalie Ahyi,
Hua-Chen Chang and
Mark H Kaplan
Microbiology and Immunology, Indiana University, 702 Barnhill Drive, RI Room 2636, Indianapolis, Indiana, 46202
Abstract
We have recently identified the ETS family transcription factor PU.1 as regulating heterogeneity in Th2 populations. To define additional factors that might contribute to Th2 heterogeneity, we examined the PU.1 interacting protein IFN-regulatory factor (IRF)-4, a transcription factor expressed in lymphocytes and macrophages. When Th2 cells are separated based on levels of IL-10 secretion, IRF4 expression segregates into the subset of Th2 cells expressing high levels of IL-10. To investigate the role of IRF4 in cytokine heterogeneity, Th2 cells were infected with retrovirus expressing IRF4. The cells overexpressing IRF4 secreted significantly higher levels of IL-10 compared to cells infected with a control vector while other Th2 cytokines were not affected. To understand the mechanism by which IRF4 regulates IL-10 expression in various Th2 cell subpopulations we used DNA pull down assays as well as co-immunoprecipitation assays to determine transcription factors that interact with IRF4. Our data shows that PU.1, IRF4 and NFATc2 form a complex in Th2 nuclear extract. The role of these complexes and their contribution towards Th2 heterogeineity will be further defined.
