Investigating the role of AP-1 activity in T cell development using mice overexpressing Batf and Batf3
Abstract
Batf proteins are members of the AP-1 family of transcription factors. Batf, the founding member of the Batf family, has been shown to be essential for the development of CD4+ Th17 cells. Batf null mice have very few Th17 cells and dramatically reduced IL-17 cytokine production. Here, I further demonstrate the role of Batf in the regulation of IL-17 producing T cells. Transgenic mice overexpressing Batf ( CD2-HA-BATF), or the highly similar Batf3 protein (CD2-Myc-Batf3 ), specifically in T cells were analyzed for CD4+ T cell defects. Results reveal an increase in Th17 cells and IL-17 production by transgenic CD4+ T cells. Additional CD4+ T cell phenotypes, such as decreased Treg cells, also were identified in the CD2-HA-BATF and CD2-Myc-Batf3 transgenic mice as well as increased serum immunoglobulin in CD2-HA-BATF transgenic mice. These data indicate that Batf proteins function to regulate the functions of multiple immune cell types. In addition to the role in Th17 cells, Batf has been shown to be important for the development and function of thymic iNKT cells. The studies presented here demonstrate a role for Batf in thymic, as well as peripheral, iNKT cells. The recent identification of IL-17 producing, NK1.1- iNKT cells together with the critical role for Batf in Th17 cells prompted an investigation of whether Batf regulates Il-17 production in iNKT-17 cells. Here, I demonstrate that CD2-HA-BATF transgenic mice have decreased NK1.1+ iNKT cells, but increased NK1.1-iNKT cells. This bias is supported by the demonstration that Batf null mice have the opposite phenotype. Furthermore, in vitro siRNA knock-down experiments in the iNKT cell line, DN32.D3, showed that reduced Batf expression results in decreased IL-17 expression. These studies demonstrate that Batf is a critical regulator of the gene expression patterns necessary for IL-17 production, both in CD4+ Th17 cells and iNKT-17 cells.
Degree
Ph.D.
Advisors
Taparowsky, Purdue University.
Subject Area
Biology|Cellular biology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.