Egr3 induces a Th17 response by promoting the development of ?? T cells.

ABSTRACT: The transcription factor Early Growth Response 3 (Egr3) has been shown to play an important role in negatively regulating T cell activation and promoting T cell anergy in Th1 cells. However, its role in regulating other T helper subsets has yet to be described. We sought to determine the role of Egr3 in a Th17 response using transgenic mice that overexpress Egr3 in T cells (Egr3 TG). Splenocytes from Egr3 TG mice demonstrated more robust generation of Th17 cells even under non-Th17 skewing conditions. We found that while Egr3 TG T cells were not intrinsically more likely to become Th17 cells, the environment encountered by these cells was more conducive to Th17 development. Further analysis revealed a considerable increase in the number of ?? T cells in both the peripheral lymphoid organs and mucosal tissues of Egr3 TG mice, a cell type which normally accounts for only a small fraction of peripheral lymphocytes. Consistent with this marked increase in peripheral ?? T cells, thymocytes from Egr3 TG mice also appear biased toward ?? T cell development. Coculture of these Egr3-induced ?? T cells with wildtype CD4+ T cells increases Th17 differentiation, and Egr3 TG mice are more susceptible to bleomycin-induced lung inflammation. Overall our findings strengthen the role for Egr3 in promoting ?? T cell development and show that Egr3-induced ?? T cells are both functional and capable of altering the adaptive immune response in a Th17-biased manner. Our data also demonstrates that the role played by Egr3 in T cell activation and differentiation is more complex than previously thought.

SUBMITTER: Parkinson RM 

PROVIDER: S-EPMC3901773 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature